Mechanism-Anchored Profiling Derived from Epigenetic Networks Predicts Outcome in Acute Lymphoblastic Leukemia

Xinan Yang, PhD1, Yong Huang, MD1, James L Chen, MD1, Jianming Xie, MSc2, Xiao Sun, PhD2, Yves A Lussier, MD1,3,4§

1Center for Biomedical Informatics and Section of Genetic Medicine, Department of

Medicine, The University of Chicago, Chicago, IL 60637 USA

2State Key Laboratory of Bioelectronics, Southeast University, 210096 Nanjing,

P.R.China

3The University of Chicago Cancer Research Center, and The Ludwig Center for

Metastasis Research, The University of Chicago, Chicago, IL 60637 USA

4The Institute for Genomics and Systems Biology, and the Computational Institute, The

University of Chicago, Chicago, IL 60637 USA

§Corresponding author

Email addresses:

XY: [email protected]

YH: [email protected]

JC: [email protected]

JX: [email protected]

XS: [email protected]

YL: [email protected]

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Abstract

Background Current outcome predictors based on “molecular profiling” rely on gene lists selected

without consideration for their molecular mechanisms. This study was designed to demonstrate that we could learn about genes related to a specific mechanism and further use this knowledge to predict outcome in patients – a paradigm shift towards accurate “mechanism-anchored profiling”. We propose a novel algorithm, PGnet, which predicts a tripartite mechanism-anchored network associated to epigenetic regulation consisting of phenotypes, genes and mechanisms. Genes termed as GEMs in this network meet all of the following criteria: (i) they are co-expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype.

Results This proof-of-concept study, which focuses on epigenetic mechanisms, was conducted

in a well-studied set of 132 acute lymphoblastic leukemia (ALL) microarrays

annotated with nine distinct phenotypes and three measures of response to therapy.

We used established parametric and non parametric statistics to derive the PGnet

tripartite network that consisted of 10 phenotypes and 33 significant clusters of GEMs

comprising 535 distinct genes. The significance of PGnet was estimated from

empirical p-values, and a robust subnetwork derived from ALL outcome data was

produced by repeated random sampling. The evaluation of derived robust network to

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predict outcome (relapse of ALL) was significant (p=3%), using one hundred three-

fold cross-validations and the shrunken centroids classifier.

Conclusions To our knowledge, this is the first method predicting co-expression networks of genes associated with epigenetic mechanisms and to demonstrate its inherent capability to predict therapeutic outcome. This PGnet approach can be applied to any regulatory

mechanisms including transcriptional or microRNA regulation in order to derive

predictive molecular profiles that are mechanistically anchored.

Lussierlab.org/publication/PGnet

Background By design, predictors of outcome based on gene expression profiles are based on gene

lists that do not require knowledge of biological processes or molecular

mechanisms[1]. Though expression arrays have been widely studied to improve prediction of clinical outcome and to aid the decision of treatment strategy for cancer, the resulting long list of genes lacking mechanistic background is thus difficult to interpret to infer their biological or clinical implications. Additionally, a poor outcome may be caused by a diversity of molecular disorders, for which the individual contribution may vary in different patients suffering from the same cancer[2]. In some cases, profiles are accompanied with follow-on enrichment studies or curated annotations that predict their possible mechanisms; while in other cases, functional clustering has been proposed to understand microarray data profiles[3]. In this manuscript, we propose a novel computational strategy based on genes associated to

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known biological mechanisms to derive mechanism-anchored expression profiles ab

initio that can accurately predict disease outcome.

We hypothesized that those co-expression modules, which are predictive of outcome,

can be computationally derived from genes known to regulate or to be regulated by epigenetic mechanisms in previous studies and from novel microarray expression specifically designed for a new phenotype for which the epigenetic mechanisms may not be well understood[4, 5]. Nearly every cancer consists of genetic mutations of the transformed cells as well as epigenetic abnormalities of non-mutational changes to

DNA that lead to alterations in gene expression[6]. While genetic abnormalities found in cancer typically affect cancer-promoting oncogenes and tumor suppressor genes, the epigenetic regulation of molecular functions involves reversible interactions which can affect gene expression such as (i) DNA methylation[7], (ii) histone modification[8],

(iii) RNA transcription and the resulting proteins[9, 10] or miRNAs[11], that influence chromatin structure. For example, histone deacetylation and the methylation of the promoter region can affect binding of transcriptional factors to these DNA regions and result in transcriptional silencing partly due to chromatin remodeling[12]. Indeed, combination therapy with inhibitors of DNA methyltransferase and histone deacetylase is under investigation in cancer[13-15]. Additionally, epigenetic events occur in the coordinated behavior of epigenetic proteins that regulate gene expressions[15]. To demonstrate the applicability of the proposed phenotype-

genotype-network” method (PGnet), a set of known biological mechanism-anchored

genes are required as the “seed” (input). Although this method can be generalized to

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other molecular mechanisms and other diseases, we focused this study on epigenetic

alterations in acute lymphoblastic leukemia (ALL).

To compute co-expression modules of genes in disease and to infer their interplay generally require the integration of data from a wide variety of sources[16, 17]. For example, some computational methods have been developed to indentify shared regulatory inputs, functional pathways and genetic interactions[2, 18-21]. We have also previously shown that co-expression patterns of genes found in expression arrays designed around specific phenotypes can be recapitulated in gene-phenotype relationships derived from database/literature mining [22]. Further, genome-scale reverse engineering of regulatory mechanisms in expression arrays have been

developed and successfully applied in mammalian cells[23]. For example, A method

called ARACNE has been shown to be effective in practice by using a mutual

information theoretic approach which focuses on direct co-expression of genes[24,

25]. However, unsupervised combinations of every molecular element that may

interact via one or more intermediaries can lead to a problem of multiplicity due to the

escalating number of comparisons and thus to a loss of statistical power. Another

method, FunNet, addresses multiplicity by combining gene expression data with Gene

Ontology[26, 27] or KEGG [28] annotations and further performs transcriptional

functional analysis over co-expression[29]. Another method, StAM, identifies

expression signature by focusing on biological processes which can characterize

subgroup of patients[2]. However, these methods are not designed to compute

regulatory networks that would also be differentially expressed in multiple phenotypic

contexts as well as co-expressed in each individual. Our approach differs from these

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previous methods in that genes are integrated to the profile signature if: i) they are associated ab initio to the biological mechanism of interest (here epigenetics), and ii) they are derived from the a non-parametric statistic taking into account comprehensive expression patterns of the every gene in the microarray rather than

from a subset of the differential-expressed ones.

We hypothesize that using supervised pair-wise measurements from microarray data

together with robust feature selection technology[1], we are more likely to construct meaningful, epigenetic mechanism-anchored, co-expression networks that are predictive of leukemia outcome. To this end, we propose a novel supervised non-parametric algorithm (PGnet) that builds a tripartite network derived from

(i) microarray expression profiles, and (ii) prior knowledge about biological mechanisms. PGnet is designed to identify sets of mechanism-anchored genes that are both consistently co-expressed across arrays and differentially expressed between phenotypic conditions.

Methods

Arrays and Phenotypes We selected a large array dataset published by the Downing research group (ALL

arrays)[30] that comprises well characterized subtypes of ALL and other clinical

phenotypes, including cytogenetic characteristics, molecular status and patient

outcomes. The details for leukemia phenotypes and sample size are provided in Suppl.

Methods.

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Epigenetic Seed Genes - ESGs (Suppl. Methods and Suppl. Table 1) Gene Ontology terms and PubMed were used to identify genes with epigenetic effects.

Genes were subsequently mapped to Affymetrix probe-sets and curated into eight categories.

Array Analyses The 132 ALL arrays were normalized with the variance stabilization and calibration

normalization (vsn) method[31] using Bioconductor[32, 33] package compdiagTools[34]. We then applied an additional inter quartile range (IQR) filter[35] to eliminate genes lacking sufficient variation across samples in expression (Suppl.

Methods).

Building a Phenotype - Gene Network (PGnet) The construction of a network comprising “Leukemia Phenotypes” (LPs), “epigenetic

seed Genes” (ESGs) and co-expressed genes required six steps (see Figure 1 and

Suppl. Methods for details on steps and equations).

Step 1a: Vector of genes co-expressed with the mechanism seed genes. All

genes that co-expressed with ESGs were sorted in a vector based on the

Pearson correlation coefficient (PCC). Results were denoted as

V , i =1,2,...48 . ESGi

Step 1b: Vector of differentially expressed Genes in ALL. At the same time,

all genes were also sorted based on their adjusted Student t-test conducted

between the phenotype of interest against the remaining pooled phenotypes.

Results were denoted as V , j =1,2,...12. Bioconductor[32, 33] package stats LPj

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was used to calculate the PCC and the package Twilight[36] was used to

calculate the adjusted t-score parameter.

Step 2: To compare two ordered lists of gene expressions, we used OrderedList[37-

39] from Bioconductor[32, 33], a non-parametric quantitative vectorial enrichment

method that we previously published, and has been shown more sensitive to detect

significant departure from a predicted distribution than semi-quantitative enrichment

approaches such as the Fisher’s Exact Test or the the Chi-square test. We calculated a

matrix of similarity scores M =(s ), where each score s assessed the pair-wise s i,j i,j similarities between two vectors. The fist vector is the ordered co-expression coefficients VESGi and the second one is the ordered differential expression statistics

VLPj. The similarity score gives higher weights to ranking extremes: the top and bottom ranks in both lists. In our method, we compared the ranking of genes in the co- expression set with those gene ranks from the phenotypic set. This resulted in a total of two comparisons for each phenotype/“seed gene” combination (correlation and anti- correlation).

Step 3: Vectorial Enrichment Optimization (VEO). To evaluate the statistical

significance of the similarity score, we generated 2,000 controls through the

permutation of each list of gene ranks and calculated empirical p-values based on random scores. Two networks were generated. In this proof-of-concept study, the arbitrary but uniform significance threshold (T =200, Suppl. Methods) of included ranks was chosen to define a set of GEMs with higher differential expression in VEO that would yield a small network (Suppl. Table 2 and Fig. 2), where the co-expressed with known “epigenetic seed genes” and phenotype-specific genes are the genes

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within the top 200 or bottom 200 in either of the two lists. An optimal length for these

ordered gene lists can also be determined by unbiased optimization methods and can

generate a larger network (Suppl. Table 3), however for the purpose of simplicity of presentation – we kept the list at T=200 for the main figures, which is within the range

of length considered biologically significant in our unbiased and more comprehensive

studies (Suppl. Table 3). In both the arbitrary threshold (T=200) and the optimal

threshold cases, the significance of PGnet were estimated by an empirical p-value of similarity scores by permutation the ranks (number of permutations=1000, Suppl.

Methods). And the adjustment threshold of significance for vectorial similarity was

conducted by controlling the false discovery rates (q-value=0.02)[40, 41] (Suppl.

Methods).

Step 4: For each significant seed gene/phenotype pair we considered these to be

“linked.” By aggregating these seed gene/phenotype pairs, we developed a tripartite network PGnet.

Step 5: Visualization of the Tripartite Network. Meaning of shapes and colors in the network: triangle (epigenetic seed genes), circle (predicted GEMs) and box

(phenotypes); red (up-regulated), blue (down-regulated) and grey for vertex of a gene had more than one linkage and was up-regulated in one condition but down-regulated in a different condition (Suppl. Methods). By color-coding the edges of the graph, we are providing a direction to each similarity vector, magenta line for correlation whereas turquoise for anti-correlation. With these vectors, one can judge how these genes express in a specific condition.

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Step 6: Biological Meaning of the Network. Using Gene ontology, we conducted an enrichment of the molecular function and biological processes among the genes identified in the PGnet biomodules in order to characterize biologically the network and we also reviewed the literature for the genes involved in the biomodules associated to BCR-ABL, T-ALL and hyperdiploidy. Thus the resulting set of genes termed as Genes significantly Expressed with the Mechanism (GEMs) in the epigenetic context of this network meet all of the following criteria: (i) they are co- expressed with genes known to be involved in the biological mechanism of interest, (ii) they are also differentially expressed between distinct phenotypes relevant to the study, and (iii) as a biomodule, genes correlate with both the mechanism and the phenotype.

Robust Predictive Network and Evaluation The predictive capabilities of the derived network were evaluated with two approaches:

(a) quantitative computational studies of the accuracy of the predictor of outcome, and

(b) qualitative comparison of the PGnet method to that of another reverse engineering one.

(a) To demonstrate the accuracy of the derived network to predict relapse, we

performed a conservative evaluation consisting of one hundred three-fold

cross-validation (CV) studies of the PGnet method. In other words, as shown in

Figure 2c, the network was derived from 2/3 of the randomly selected patients

and the evaluation was conducted on the remaining third. The random selection

was conducted to conserve the respective group sizes (normal, cancer) and was

considered a more adequate and severe control[42]. This procedure was

repeated one hundred times on different random resamplings. Two different

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predictive methods were used as well: (i) Prediction Analysis for Microarrays

Class Prediction[43] (PAM) that does not involve any machine learning and (ii)

the Support Vector Machine[44] (SVM) (Suppl. Methods and Suppl. Fig. 2).

The resulting receiver operating characteristic (ROC) curve, area under the

curve (AUC) and corresponding p-values were calculated by the

Bioconductor[32, 33] package verification[45]. A robust molecular signature is

one that repeatedly appears by random sampling[1]. We further identified the

GEMs correlated with the ESGs that were identified as robust[1]. The robust

ESGs refer to those GEMs that were among the top 5% frequencies in the one

hundred iterations of the 3-fold cross-validation (Figure B in Suppl. Methods).

Figure 3 illustrates the sub-network associated to the comparison between

“Relapse” and the “continuous complete remission - CCR” phenotypes.

(b) Finally we compared our results to those obtained by a straightforward

reverse engineering method (ARACNE).

Results Seventy-one distinct epigenetic seed genes were identified in the literature review and denoted as “seed gene” candidates for input in PGnet (Suppl. Table 1). In the 132

ALL arrays, 7,256 out of 12,997 unique genes and 48 out of the 71 subset of ESGs satisfy the IQR filter (bolded genes in Suppl. Table 1). The 48 ESGs are thus enriched ab initio among genes differentially expressed in ALL samples suggesting a biological relevance in ALL (p=5%, Fisher’s Exact Test).

We built a gene-phenotype network specific for epigenetic genes clusters in ALL as shown in Figures 2a and b. The derived network comprises 33 significant nodes,

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including eight clinical subtypes of ALL and two outcome conditions (LP, vertex in

yellow box), 23 epigenetic seed genes (ESG, yellow triangle) and 535 genes that co- express with ESGs (GEM, grey circle). Three of these ESGs and 299 GEMs are up- regulated in association to their phenotype(s) as compared with their expression associated to the remaining pooled phenotypes, while 14 ESGs and 203 GEMs are

down-regulated. In addition, 6 ESGs and 33 GEMs were up-regulated in one phenotype but down-regulated in a different phenotype, which are phenotype specifically differential expressions (see Step 3 of Methods). A summary of predictions is provided in Suppl. Table 2. These 23 ESGs genes are highly co- expressed with epigenetic genes and also highly differentially expressed in distinct

ALL phenotypes groups (CBX1, CBX5, CBX6, CBX7, PHLDA2, BAZ2A, BAZ2B,

MYST2, MYST4, MECP2, SMARCA2, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC9,

SMARCA4, SMYD3, SUV39H1, DNMT3A, DNMT3B, PRDM2 and MBD2).

To validate the prognostic ability of the genes in PGnet associated with leukemia relapse, we performed one hundred three-fold cross-validations in two ways (Suppl.

Methods and Suppl. Fig. 2). Using the PAM classification that does not require machine-learning, the predictions were accurate (AUC=0.65, p=3%, Suppl. Fig. 3).

We also conducted a severe control by randomly selecting genes differentially expressed in the array and the p-values of the derived predictors ranged from 12% to

67%, further corroborating that the epigenetic network derived by PGnet is associated to the relapse outcome. Using SVM machine-learning to improve the predictions in a

3-fold cross over design, PGnet achieved a AUC=0.67 (p=1.6%) (Figure 3 in this manuscript). Precision and recall of the predictor in cross-validation studies are also

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significant (Suppl. Fig. 4). The evaluation confirmed the detection of co-expression biomodules associated to epigenetic alterations can be utilized in the identification of

ALL with poor prognosis[46]. Supplementary Table 5 reports 52 robust GEMs

together with 3 robust ESGs (CBX5, SMARCA4 and DNMT3A) associated with

leukemia relapse (Suppl. Methods).

We further proceeded to identify biological enrichment in the distinct sets of genes

associated with response to therapy and long-term maintenance of disease remission.

There were 4 ESGs and a total of 39 GEMs associated with the phenotype “Relapse”,

such as CCNA2, BUB1, MAD2L1, CDC45L and CCNB2, etc, which were significantly

enriched in one GO term: ATP binding (hypergeometric p = 3.5x10-6, Suppl. Table

4). Interesting, ATP has been reported as treatment target of murine leukemic cells in vitro to reduce the number of leukemic clonogenic cells[47].

Of note, PGnet is designed to discover mechanism-anchored biomodules that are phenotype-specific and that are consistently co-expressed across every patient. Figure

4 shows genes that are down-regulated in one phenotype and up-regulated in another phenotype and vice-versa (Suppl. Table 3). In PGnet, 67 genes are involved in the expressional biomodules that are co-expressed with HDAC4 and DNMT3B, and yet are differentially expressed between “T-ALL” and “BCR-ABL” phenotypes. Enrichment analysis of these genes revealed only one significant enrichment: “MHC class II receptor activity” (GO:0032395, hypergeometric p-value=1.6x10-11, Suppl. Table 4).

Further identification of the intersected regulation function of these epigenetic bio- modules requires experiments in vitro.

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The GEMs derived from PGnet can distinguish their associated phenotype in addition

to be co-expressed with their associated seed gene on transcript level. As an example in this study, Supplementary Figure 5 shows that the expression of 61 GEMs can

clearly distinguish samples of “Hyperdiploid>50” from other ALL samples. There

were 4 ESGs associated with the hyperdiploid karyotypes by PGnet. HDAC6 is a class

IIB histon deacetylase and identified as target of anti-leukemia therapy[48]. Inhibition

of HDAC6 disrupts the association of HSP90 with its chaperon proteins, resulting in

ubiquitylation of certain oncogenes, such as Bcr-Abl[49]. Three other genes were also down-regulated (SMARCA4, BAZ2A and SMARCC2): SMARCA4 is a drug target candidates in hyperdiploid multiple myeloma[50]; BAZ2A is a novel nucleolar

chromatin remodeling machine[51], and SMARCC2 was among the top discriminating

genes in the good prognosis subgroup of MLL[52]. Moreover, GEMs identified by

PGnet significantly enriched among the top-100 marker genes in previous genome-

scale studies of ALL (Fisher’s test p<2x10-16, Suppl. Table 6).

Discussion

Comparison of the derived network with other computational methods ARACNE[24, 53] software was used to reverse engineer the transcriptional network in

two ways. First, by providing the genes expression data for entire ALL samples as

input, we compared our GEMs with genes identified by ARACNE (Result is given in

Suppl. Table 7). We provided ARACNE our 48 epigenetic seed genes and the

expression data for samples in each phenotype as input, irrespectively. Subsequently,

we got 12 different phenotype specific gene-gene networks. Each ARACNE network

detects thousands of genes that with significant (p<0.05) mutual information (MI) with

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inputted ESGs. By design, a majority of the genes detected by ARACNE are not

phenotype specific. GEMs predicted by PGnet overlap with ARACNE’s prediction for

31 of 33 ESGs (Suppl. Table 8). However, PGnet differs from ARACNE in that it

provides phenotypic information left out in ARACNE.

ARACNE, FunNet and PGnet provide co-regulation networks as an output and are

thus "related"; however, they differ in several important ways: (i) PGnet and FunNet

combine supervised technology and non-parametric methodology while ARACNE

uses information theory; (ii) inputs to PGnet are expression levels and phenotypic

associations of interest such as seed genes whereas FunNet requires full expression

together with a reference list of all transcripts to be analyzed and ARACNE uses

expression data exclusively; (iii) FunNet abstracts transcriptional functions from co-

expression layer; and consequently (iv) PGnet’s output is a tripartite network consisting of co-regulated genes and clinical/genetic characteristics of interest while

ARACNE's or FunNet’s outputs are uni-partite graphs. (v) The significant threshold of

PGnet relates to the complete ordering of all genes to be analyzed whereas the significant threshold of FunNet is related to the co-expression of single gene. (vi)

PGnet not only provides a degree of association between phenotypes but also sheds light on whether there was concordance in the directionality of the changes in expression level.

PGnet parallelizes two input vectors and finds sets of GEMs via vectorial enrichment optimization. Using measurements of differential expression and co-expression together, PGnet is more reliable in discovering phenotype-specific biomodules that are consistent across every patient than a simplified method that analyzes the expressed

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pattern of the epigenetic seed genes (ESGs) alone. First, a simplified method identifies

none of GEMs from PGnet. However, we have shown some evidence indicating that the GEMs are more likely to be involved in specific epigenetic events than those directly calculated to be correlated to a phenotype of interest. Second, simpler alternate methods relying on co-expression or differential expression separately would identify only a the subset of ESGs from PGnet (data not shown), because these methods use an

arbitrary threshold for significance of each gene and neglect the joint analysis of co-

expression patterns with those of differential expression. In contrast, the “ESG-

phenotype” linkage, which we proposed in PGnet, would be significant even if the

epigenetic seed gene itself is not “significantly” differentially expressed in the linked

phenotype (for instance, the seed genes that are not self-linked in Suppl. Fig. 1).

Biologically, PGnet is an attractive technique as we know that mechanism-related genes have similar patterns of expression[4, 20], and pathological mechanisms are easier to understand than genes by clinicians. Additionally, the non-parametric rank- correlation algorithm that we previously developed for Bioconductor can use the full range of the expression data for discovery instead of arbitrary statistical cut-offs[37-

39]. We have extended it to derive phenotype-genotype correlations based on prior knowledge in addition to gene expression. Moreover, this tri-partite network allows to view genes for which the expression is specific to a phenotype of interest and also anchored to a biological mechanism.

Future studies and limitations Epigenetic gene regulation is one among many possible mechanisms involved in disease-specific gene aberrant activation. Better predictors of outcome can be

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developed using a more comprehensive number of biological mechanisms. The PGnet method could be expanded to a broader variety of biological mechanisms in order to provide more accurate mechanism-anchored profiles that predict therapeutic outcome

(e.g. transcriptional and microRNA networks[54], Gene Ontology terms, KEGG, etc), however additional methods are required to control for multiplicity of mechanism while preserving accuracy of the derived tripartite networks. In addition, this PGnet is a supervised method that relies on prior knowledge about seed genes or gene products that regulate epidemic processes. Therefore, PGnet may "skew" the network accordingly, which may reflect only subset of the real regulatory relationship. Further improvement for finding disease associated and seed-gene regulated genes will likely require a refined assessment of co-expression, e.g. mutual information[24, 55], instead of linear Pearson coefficient[37]. By design, PGnet identifies biomodules that are consistently co-expressed with the mechanism seed genes across all patient samples.

However, there could exist mechanisms that are only co-expressed in some specific phenotypes and otherwise the co-expression patterns are lost. These particular biomodules may also contribute to mechanism-anchored predictors and require further methodological developments for their ascertainment. Future evaluations comparing the PGnet-derived predictors in other datasets are required, and we intend to proceed with multi-mechanism profiling that would in theory achieve higher precision and recall.

Conclusion We introduced and evaluated a novel algorithm, PGnet, to identify mechanism- anchored co-expression networks and to predict therapeutic outcome. PGnet differs

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from previous reverse engineering methods in that it provides a more comprehensive output consisting of a tripartite network of expression similarity between genes, biological mechanisms and clinical phenotypes. Additionally, statistical significance is

conducted over expression ordering inclusive of the complete array.

Trained on epigenetic mechanisms, PGnet accurately classified patients in the

leukemia subtype and the relapse group, and these results suggest that a more

comprehensive multi mechanism-based profile may achieve higher accuracy scores.

The proposed method is scalable, in principle, to other mechanisms such as

transcriptional networks, microRNA-regulated or Gene Ontology classes. In addition,

the produced “similarity linkages” between mechanisms and genes comprise

magnitude and direction (correlated or anti-correlated), which could also be utilize to infer regulation (activation or suppression)[15].

Acknowledgements This work was supported in part by the The Cancer Research Foundation, the NIH

National Center for Multiscale Analyses of Genomic and Cellular Networks

(MAGNET) 1U54CA121852, and the Natural Science Foundation of China 60771024,

60121101 and. We thank Dr. Richard Sheuermann for his contribution to the interpretation of the network. We also thank Dr. Zuhong Lu for his contribution in developing the epigenetic gene list. We would also like to acknowledge Matthew

Crowson for his assistance in the revision of this manuscript.

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Figures

Figure 1 - Design of PGnet Methods.

Two sets of data are required to construct the network: (i) VESG lists are produced by

analyzing the known epigenetic “seed genes” using the pairwise standard Pearson

correlation coefficient of the vsn normalized gene expression levels between ESG and all genes gn that meet the IQR filter criteria across all samples where genes gn

(n=1,…,N), (ii) VLP lists are derived by analyzing the gene’s differential expression in each phenotype of interest and evaluating its significance with an adjusted t-test. The rows in both VESG and VLP lists represent every genes in the microarray that meet the

IQR filters, whereas the columns are either epigenetic seed genes in the VESG lists or

phenotypes in the VLP lists. We then use the PGnet methodology to develop a similarity

vector between the epigenetic seed gene and a phenotype. We calculated the vectorial

similarity between each pair of ordered expression of gene lists using a previously

algorithm that we published, orderedlist (Suppl. Methods)[37]. The result is a ranked

- 24 -

list of genes that are significantly associated based on their respective VESGi and VLPj. We build a gene-phenotype network where relationships are similarity scores (Fig. 2).

Legend: g: gene with microarray expression; ESG: epigenetic seed gene; LP: leukemia phenotype.

Figure 2 - Network Modelling of Epigenetic genes – phenotypes in ALL derived from PGnet.

(a)

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(b)

(C)

The complete tripartite network produced by PGNet is available as Suppl. Fig. 1 and

Suppl. Table 2. Here, panel (a) shows a bipartite subset of 33 statistically significant associations linking 23 distinct epigenetic seed genes (ESGs, yellow triangle) to - 26 -

10 distinct leukemia phenotypes (yellow squares). Distinct background colors of ESG gene names indicate distinct molecular function or biological process related to or targeted by epigenetic regulation (Suppl. Table 1). Two LPs and one ESG with asterisk were selected to show the details of a biomodule derived by PGnet (Figure 4).

Red genes are those for which the expression is up-regulated in the associated ALL phenotype, while blue ones are with down-regulated expression, and grey ones are related to more than one phenotype with alternate up-down regulations (details of the full network in Suppl. Table 2). Panel (b) shows a tripartite network that includes

GEMs (grey circles) and focuses on the circled subset of Panel a: the “ALL relapse”.

Panel (c) is a robust sub-network associated to ALL outcome (relapse vs. continuous complete remission (CCR)). Three ESGs and 53 GEMs were obtained by 100 repetitions of 3-fold cross-validation of PGnet operating on the subset of ALL arrays comprising 87 patients experiencing either “CCR” or “relapse” (n>32, details in

Suppl. Methods). Note that ALL subtypes associated PGnet in panel a) and b) were derived from all 132 patients (in this case the biomodules of the sub-network 2b pertain to patients with relapse and not everything else). The robust sub-network in panel c) was conducted for training a predictor of outcome. Only 87 out of the 132 samples contained outcome information related to ALL relapse (“relapse” or “CCR” of ALL). Please note that some patients did have an outcome of secondary AML, a distinct form of leukemia, and were excluded from panel 2c because this disease occurs at a later stage and the authors of the dataset did not disclose the outcome of

ALL for these patients. Thus the biomodules of Figure 2c overlap partially with those of Figure 2b.

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Figure 3 - Evaluation of the Outcome Predictor of “ALL Relapse” derived from the Mechanism-Anchored Expression Profile obtained by PGnet.

True Positive Rate Positive True AUC=0.67 P=1.6%

False Positive Rate

The 87 leukemia patients with “CCR” or “relapse” information were randomly divided

into three folds, two of which were used to identify the predictor of outcome (“CCR”

vs. “relapse”, Figure 2c). The predictor consisted of GEMs and ESGs associated to

“relapse” to train a linear SVM model, and the remaining one was used as a blinded

test set. Three-fold cross-validations were repeated 100 times. The resulting Receiver

Operating Characteristic (ROC) curve, the area under the curve (AUC) and

corresponding p-values were calculated by Bioconductor package verification.

Horizontal and vertical “error bars” represent the 95% confidence intervals of the

predictor. Regions where the error bars are above the diagonal line represent a better

prediction than chance. Overall, the AUC was significantly different than that of a

random predictor of “ALL relapse” (P=1.6%).

- 28 -

Figure 4 - Details on the expression biomodule associated with BCR-ABL and T- ALL phenotypes and the epigenetic mechanism of HDAC4.

The ESG (gene symbol in red) is positively correlated with part of its GEMs (n=10) as

down-regulated in “BCR-ABL” and up-regulated in “T-ALL”, and negatively

correlated with another parts of its GEMs (n=36). 47 genes were derived from PGnet

under optimal threshold (Suppl. Table 3). The standard full agglomerative

hierarchical clustering was performed on Spearman’s rank correlation distance of

normalized expression levels. The resulting heatmap was drawn using Bioconductor

package made4.

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Additional files Supplementary Methods – Supplementary Methods

Supplementary Figure 1 – PGnet: significant “phenotypes in ALL – GEMs - epigenetic seed genes”

Supplementary Figure 2 – The Design of the two Evaluations (A and B)

Supplementary Figure 3 – The ROC curve of the computational evaluation method B of PGnet-predicted GEMs and ESGs signature associated with ALL relapse

Supplementary Figure 4 – The precision_recall results of the computational evaluation A of PGnet-predicted GEMs and ESGs signature associated with ALL relapse

Supplementary file Figure 5 – Expression pattern of ALL phenotype “Hyperdiploid>50” specific GEMs by PGnet

Supplementary Table 1 – The eight categories of epigenetic key terms and their corresponding 71 epigenetic seed genes

Supplementary Table 2 – Thirty-three significant “LP-ESG” linkages contributed by corresponding GEMs (parameter T=200)

Supplementary Table 3 – The predicted GEMs of 117 significant “LP- ESG” linkages based on optimal parameters (Ts)

Supplementary Table 4 – The significantly enriched GO items among the predicted GEMs that linking to phenotypes of interested

Supplementary Table 5 – Robust GEMs and ESGs Predictive of Leukemia Relapse

Supplementary Table 6 – Previously reported facts about predicted GEMs

Supplementary Table 7 – Comparison GEMs in PGnet with genes identified by ARACNE

Supplementary Table 8 – Comparison of the results from ARACNE and PGnet for leukemia phenotypes

- 30 -

Supplementary Methods

1. Dataset We selected a well-studied public gene expression dataset[1] to check the global epigenetic

protein behaviors in pediatric acute lymphoblastic leukemia (ALL). The leukemia phenotypes

(LPs) in this dataset comprise of clinical subtypes, cytogenetic characteristics, molecular status and patient outcome. In this study, only the phenotypes with more than 3 samples were included which are: i) ALL genetic markers and subtypes, including t(1;19)(E2A-PBX1), t(12;21) (TEL-

AML1), t(9;22) (BCR-ABL), leukemia with less diploid (Pseudodip), hypodiploid 47-50

(hypodip), more than 50 chromosomes (hyperdiploid>50), and with normal diploid (hereafter referred as “normal”). ii) The patient outcome phenotypes, including complete clinical remission

(CCR), relapse and treatment-induced AML (2nd AML). The sample size in each phenotype is given in bellow Tab le A. Expression raw data were downloaded from: http://www.stjuderesearch.org/data/ALL3 and the phenotypes of samples were

downloaded from a previous study of the

author[2]: http://www.stjuderesearch.org/data/ALL1/all_section2.html#section2_top.

Table A. Leukemia phenotypes and sample sizes (n>3)

T- MLL BCR- E2A- TEL- Normal Pseudodip Hypodip Hyperdip>50 CCR Relapse 2ndAML

ALL ABL PBX1 AML1

14 20 13 18 20 10 11 4 18 71 16 6

2. Finding Epigenetic Seed Genes (ESGs) It has been proven in vitro that promoter methylation of regulatory genes can result in dys-

expression of other genes and contribute to disease-specific phenotype[3]. To derive the

epigenetic protein’s regulation of gene expression, we focused on genes whose translation

Suppl. Methods – page 1

products were associated with four major types of epigenetic modification by literature

reviewing:

• DNA methylation, including 7 gene symbols: MBD[4], SETDB[4], MECP[4], ZBTB33[5],

DNMT[6] and SMARC[7];

• genomic imprinting, including IGF2 [8] and genes in GO category “GO:0006349”;

•histone modification, including 10 symbols of genes: HAT1[9], DOT1L[9], MYST[9],

HDACs[8], SUV39Hs[10], SET[10], EHMT [10], PRDMs[10], SMYD3[11], CBX[12], “histone

acetyltransferase” and ash1[10] ;

• chromatin remodeling: SWI/SNF[13] enzymes and BAZ2[14].

A total of 17 symbols (Suppl. Table1, column 2) involving eight categories of epigenetic

modification (Suppl. Table1, column 1) were used to search epigenetic seed genes in this ALL

array data[1].

3. Mapping Epigenetic Seed Genes to Affymatrix Probe-sets The mapping between epigenetic seed genes and affymatrix probe-sets was based on LocusLink

information and GO annotation (GO db 2.2.0), using the R-package[15] hgu133a (version

1.16.0). A total of 71 unique genes were found within the array (Suppl. Table 1).

4. Preprocessing the Expression Profiles The expression CEL files were scaled with asinh-transformation after variance stabilization and calibration normalization (vsn) [16], using Bioconductor package compdiaglTools[17]. The

asinh-transformation is similar to the log2-transformation for large intensities, but it is less steep

for low intensities.

We then applied the inter quartile range (IQR) filter[18] which eliminated genes leacking

sufficient variation in expression across samples. The variation filter involved the following four

Suppl. Methods – page 2

steps: 1) removing probe-sets whose average expression intensities were below than the average

background intensities; 2) removing probe-sets that could not be mapped to any Entrez gene ID,

which resulted in 21,382 probe-sets; 3) removing probe-sets with a IQR measurement lower than

the median IQR values of remaining probe-sets, which resulted in 10,691 probe-sets; 4) selecting

the unique probe-sets for each gene (Entrez) with the largest IQR value, using the Bioconductor

package genefilter. The last step reduced the number of our hypothesis testing to 7,256 genes,

and improved the precision of test on microarray profile with fewer samples by eliminating

thousands of variables. It precision improvement also due to that our “seed gene - phenotype”

relation was derived from comparing two vectors (ordered gene lists), and the probe-sets for the

same genes might perform similar and thus bias the whole compared vector, for example, all in

the top ranks.

5. Construction of the ESG-GEMs-LP Network The construction of the gene-condition network required a series of five steps. Step 1a: After

inputting the 48 out of 71 epigenetic seed genes (ESGs) that passed the IQR filter, the pairwise

standard Pearson correlated coefficients of the gene expression levels between each gene in the

array and every one of the 48 epigenetic genes were then calculated. Thus we got 48 vectors of

co-expression coefficients VESGi, i=1,2,…48. Note that the statistics of the probe-sets that

designed for the same gene were not independently measured, but were measured by selecting the probe-set with the largest value of IQR for every gene. We did this selective measurement for

each gene with multiple probe-sets because probes in Affymetrix chips do not work equally well,

and we did not expect the measurement of the same gene bias the ranks on one hand or appear

controversial up-/down-regulated on the other.

Step 1b: A one-vs.-all differential expression test was performed for each of the 12 leukemia

Suppl. Methods – page 3

phenotypes (LPs) with a sample size more than three. The “one-vs.-all” means after dividing the

leukemia data into two sets based on whether they contained the phenotypic condition of interest,

a two-group statistic was then calculated, which resulting in 12 vectors termed as VLPj,

j=1,2,…12. Each of such vector was the adjusted t-statistics for differential expression in one LP.

Note that only 93 samples had outcome information and were used when evaluating the differential expression in the conditions of outcome (Relapse, CCR and 2ndAML).

Step 2: Then a matrix of similarity scores M =(s ) was calculated, where each score s s i,j i,j assesses the pair-wised similarities between the ordered co-expression coefficients and the

ordered differential expression statistics. The similarity was tested based on a previous published

algorithm[19, 20] which compares first order with second order, and with second reverse order

' as well. A preliminary similar score si, j is given in formula 1:

1 α s' = s'(V ,V ) = w [O (V ,V ) + O ( f (V ), f (V ))] , (1) i, j ESGi LPj ∑ n n ESGi LPj n ESGi LPj 2

where function On (V1,V2) counts the number of overlapping between two ordered gene lists

(vectors) within their n leading orderings, and function f (V) flipps the vector V upside-down.

α −nα The weight wn = e is (not necessarily strictly) decreasing along ranks n and hence how a

partial intersection sizes on both ends of the orders can be controled by turning the parameter

α[19].

The consequence enrichment analysis was performed not only for any pair of vectors (straight similar, the first half of the formula 2), but also for one vector with another reserved vector

(reversed similar, the second half of the formula 2). This resulted in a total of two comparisons for each phenotype/seed gene combination. Thus the general delineation of similarity score Si,j

considering about both ordering and reverse ordering is:

Suppl. Methods – page 4 s = s(V ,V ) = max(s'(V ,V ),s'(V , f (V ))) . (2) i, j ESGi LPj ESGi LPj ESGi LPj

If a “ESGi-LPj” pair was significantly straight similar, there must be a group of genes co- xpressed with seed genes (ESG) whose up-regulated genes in LPj were enriched with the co- expressed genes with ESGi, and (or) whose down-regulated genes in LPj were enriched with the anti-coexpressed genes with ESGi. Vice verse, for a reversed similarity, the enrichment were come between up-regulated genes in LPj with the anti-coexpressed genes with ESGi, and (or) whose down-regulated genes in LPj with the co-expressed genes with ESGi.

Step 3: Vectorial Enrichment Optimization (VEO). After performing random permutations

(permutation times were 2000) by randomly assigning the actual ranks to all genes, 1000 random scores were generated, and then an empirical p-value was calculated.

There were two parameters’ optimizations, one is the threshold of significance (TS), and another is the threshold of included ranks (T). A significance threshold (TS =0.01) was chosen to define significant similar pairs. The optimization of included ranks (Opt.T) was discussed in our previous publication[19], which is the one that achieves the lowest empirical p for a given range of candidates (100, 150, 200, 300, 400, 500, 750, 1000, 2000, 2500) based on 1000 random scores. The VOE is applied for each pair of vectors, and adjustment threshold of significance (TS) for vectorial similarity was conducted by controlling the false discovery rates.

Two networks were subsequently generated. The uniform significance threshold of included ranks (T=200) was chosen to define a highly significant score in VEO that would yield a small network consisting of 23 ESGs and 10 LPs (Suppl. Table 2 and Fig. 2 of the main document).

An unbiased data-driven optimized parameter leading to a larger network consisting of 46 ESGs and 11 LPs (Suppl. Table 3) were also generated. Q-value[21, 22] was calculated using the

Suppl. Methods – page 5

Bioconductor package Qvalue to estimate false discovery rate (proportion of false positives incurred) at each level of p-value to be considered as “significant”. The estimated q-values were given in Suppl. Table 3. Our analysis showed that a cut-off of q-value smaller than 0.02 would identify significant similar pairs of vectors at a zero false discovery rate (Figure A).

Step 4: For each significant pair of vectors that one corresponding to seed gene and another correspond to phenotype, we considered the epigenetic seed gene (ESG) and leukemia phenotype

(LP) to be “linked.” For simplification, we hereinafter called the similarity between two ordered lists as a “similarity between the corresponding ESG of and LP”.

Step 5: Visualization. The hubs of our tripartite network are either epigenetic seed genes

(triangle colored according to the ESG category) or leukemia phenotypes (box colored in yellow).

The predicted epigenetically regulated genes (circle) were colored in grey. As mentioned in Step

2, formula 2, we compared the “straight similar” with “reversed similar” for any pair of vectors

and took the maximum. If one vector significantly ordered as another vector, we linked them

with magenta line while a turquoise line links the reversely ordered twos. In addition, every

vertex of gene was colorful annotated according to its average change in expression to its linked

phenotype (Red indicated up-regulation and blue for down-regulation). If a vertex of a gene had

more than one linkage and was up-regulated in one condition but down-regulated in a different

condition, it was annotated by grey. By color-coding the graph, in essence we are providing a

direction to the similarity vectors. With these vectors, one can judge how these genes express in

a specific condition. For example, in Figure 2a of the main document, the vertex of HDAC9 is

grey, as it is straight similar to the “Relapse” vertex and reversed similar to the “CCR” vertex.

Correspondingly, gene HDAC9 is up-regulated in the sample phenotype group as “Relapse”, but

down-regulated in the CCR sample group.

Suppl. Methods – page 6

Figure A. Three plots describe the estimates q-values for empirical p-values. a) q-values

versus the p-values; b) The number of significant tests versus each q-value cutoff; c) The number

of expected false positives versus the number of significant tests. The red lines show that a cut-

off of q-value smaller than 0.02 would identify none false discovery for our resulting pairs of

vectors.

6. Evaluation Table B: Two ways to evaluate PGnet

Area of Evaluation Method

Examination of the putative gene GO and PubMed databases were searched for corroboration of functions predicted in the network results in PGnet

Evaluation A: uses PGnet to identify predictors and trained linear Examination of the prognostic Support Vector machine (SVM)[23] model to do classify (Suppl. ability for partial profiling of the Fig. 2 panel a). mechanism-anchored network by Evaluation B: uses PGnet to identify predictors and Prediction 100 iterations of three-fold cross- Analysis for Microarrays Class Prediction (PAM)[24] as classifier validation (Suppl. Fig. 2 panel b).

Tab le B provides a summary of our validation methods. To examine the putative gene functions

predicted in the network, we searched PubMed resources. We also did hypergeometric

Suppl. Methods – page 7 evaluation for the GO item enrichment among the GEMs that linked to certain leukemia type.

The background gene set was the genes detected by the chip (Affymetrix hgu133a.db_2.2.0). We used Bioconductor[25, 26] package GOstats[27] to do the enrichment analysis for molecular function terms in GO database (GO.db_2.2.0). And after further controlling the false discovery rate, the significant GO items were reported for genes linked to LP of interested (Suppl. Table

4).

To examine the prognostic ability for partial profiling of the epigenetic mechanism anchored network, 3-fold cross validation (CV) was run 100 repeats on the 87 samples with “relapse” or

“continuous complete remission - CCR” following-up records in this dataset[1]. Please note that some patients did have an outcome of treatment-induced AML, a distinct form of leukemia, and were excluded here in the evaluation procession because this disease occurs at a later stage and the authors of the dataset did not disclose the outcome of ALL for these patients. Each running of

CV adopted PGnet to select “CCR” associated features on two-thirds of random sampled stratified arrays and did classification on the remaining one-third arrays by either trained linear support vector machine[23] (SVM) model or directly running Prediction Analysis for

Microarrays Class Prediction (PAM)[24]. The prediction accuracy was viewed by Receiver operating characteristic (ROC) curve and the precision-recall plots (Suppl. Fig 3 and Suppl. Fig

4).

To further assess the performance of PGnet feature selection on leukemia relapse prediction, we randomly picked the same number of genes as PGnet selected from 7,256 background genes, and observed the area under a curve (AUC) value for each cross-validation.

The ROC curve is widely used to direct-view the performance of any rule for two-group classifying problem. The sensitivity and specificity of validations therefore were plotted as ROC

Suppl. Methods – page 8

curve for each set of marker genes using Bioconductor package ROC. AUC is viewed as a

measure of a prediction's accuracy, i.e. a measure of 1 would indicate a perfect model, while a

measure of 0.5 would theoretically indicate a random prediction[28, 29]. The p-value of AUC

were estimated using Bioconductor[25, 26] package verification[29]. And the 95% confidence

intervals were estimated by calculating the sensitivity and specificity values after 1000

bootstrapping the observation and prediction.

There were 1,069 out of 7,256 genes were called at least once during the 100 iterations in

Evaluation A. Among them, 55 genes including 3 ESGs (Suppl. Table 5) were high-frequently

identified (x>32, the 95% quantitle of observed frequencies, Figure B) and hereafter were called

as “robust features”[30].

Figure B. Histogram of the frequencies of genes to be identified by PGnet during the 100 iterations of cross-validation (Table B, Evaluation A). The red dash line indicates the 95% quantitle of observed frequencies which is 32. The 55 robust signatures are the genes that were called more than 32 times (Suppl. Table 5).

7. Comparison with Another Reverse Engineering Technology - ARACNE ARACNE[31] is an approach for reverse engineering of cellular networks that overcomes the

Suppl. Methods – page 9

limitation of co-expression involved in indirect interactions[32], by using an Mutual Information

(MI) theoretic approach, and has been shown effective in practice[33]. This method has been

proven effective in identifying bona fide transcriptional targets in mammalian networks[33, 34].

We used ARACNE program for the reverse engineering of transcriptional networks from

preprocessed microarray data and further identified a short range of direct interactions from the

long range of correlated variables. For the expression levels of 132 leukemia samples,

ARACENE determined a kernel width from the data size, the most important parameter for the

Gaussian kernel estimator of MI which scaled as a power-law of the sample size, to be 0.499. As a result, our technique overlaps with ARACNE however has the added benefit of providing phenotypic information (results in Suppl. Table 7).

ARACNE is not designed to produce tripartite networks, while PGnet is. In other words, the

ARACNE method allowed us to compare only the ESG-GEMs relationships, not the ESG-GEM-

LP ones. We thus focused on the comparable components of the networks for the evaluation based on ARACNE. To further compare the two technologies in small sample size, we supplied

ARACNE with our 48 epigenetic seed genes, and the expression data for samples of different phenotype, phenotype respectively (inputs). Thereafter, ARACNE produced 12 different phenotype specific gene-gene networks. We took the including criteria for MI as p-value<0.05,

15% DPI-tolerance and kept other default parameters of ARACNE and compared the results with PGnet (Suppl. Table 8).

Reference 1. Ross ME, Zhou X, Song G, Shurtleff SA, Girtman K, Williams WK, Liu HC, Mahfouz R, Raimondi SC, Lenny N et al: Classification of pediatric acute lymphoblastic leukemia by gene expression profiling. Blood 2003, 102(8):2951-2959. 2. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A et al: Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression

Suppl. Methods – page 10

profiling. Cancer Cell 2002, 1(2):133-143. 3. Hopfer O, Komor M, Koehler IS, Schulze M, Hoelzer D, Thiel E, Hofmann WK: DNA methylation profiling of myelodysplastic syndrome hematopoietic progenitor cells during in vitro lineage-specific differentiation. Exp Hematol 2007, 35(5):712-723. 4. Roloff TC, Ropers HH, Nuber UA: Comparative study of methyl-CpG-binding domain proteins. BMC Genomics 2003, 4(1):1. 5. Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, Daniel JM, McCrea PD: Non- canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol 2004, 6(12):1212-1220. 6. Hermann A, Gowher H, Jeltsch A: Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci 2004, 61(19-20):2571-2587. 7. Moinova HR, Chen WD, Shen L, Smiraglia D, Olechnowicz J, Ravi L, Kasturi L, Myeroff L, Plass C, Parsons R et al: HLTF gene silencing in human colon cancer. Proc Natl Acad Sci U S A 2002, 99(7):4562-4567. 8. Feinberg AP, Tycko B: The history of cancer epigenetics. Nat Rev Cancer 2004, 4(2):143-153. 9. McManus KJ, Hendzel MJ: Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol 2003, 23(21):7611-7627. 10. Kim KC, Geng L, Huang S: Inactivation of a histone methyltransferase by mutations in human cancers. Cancer Res 2003, 63(22):7619-7623. 11. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y: SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 2004, 6(8):731-740. 12. Bernstein E, Duncan EM, Masui O, Gil J, Heard E, Allis CD: Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol Cell Biol 2006, 26(7):2560-2569. 13. Roberts CW, Orkin SH: The SWI/SNF complex--chromatin and cancer. Nat Rev Cancer 2004, 4(2):133-142. 14. Zhou Y, Santoro R, Grummt I: The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J 2002, 21(17):4632-4640. 15. Ihaka R, Gentleman R: R: a language for data analysis and graphics. . Journal of Computational and Graphical Statistics 1996, 53 299-314. 16. Huber W, von Heydebreck A, Sultmann H, Poustka A, Vingron M: Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 2002, 18 Suppl 1:S96-104. 17. Scheid S. JJaLC: A toolbox for performing and illustrating microarray data analyses – user’s guide to the R package compdiagTools. CompDiag Tech Rep 2005, 01 Mar. 18. von Heydebreck A, Huber W, Gentleman R: Differential expression with the Bioconductor Project. Bioconductor Project Working Papers 2004. 19. Yang X, Bentink S, Scheid S, Spang R: Similarities of ordered gene lists. J Bioinform Comput Biol 2006, 4(3):693-708. 20. Lottaz C, Yang X, Scheid S, Spang R: OrderedList--a bioconductor package for detecting similarity in ordered gene lists. Bioinformatics 2006, 22(18):2315-2316. 21. Storey J: A direct approach to false discovery rates. Journal of the Royal Statistical Society, Series B 2002, 64:479-498.

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Suppl. Methods – page 12

Supplementary Figure 1. PGnet: significant “phenotype in ALL – GEMs - Epigenetic seed genes”. The predicted “GEMs” (grey circles) are co-regulated with their corresponding epigenetic seed gene (ESGs, triangles) and co-differentially expressed in linked leukemia phenotypes (LP, yellow boxes). Red genes are up-regulated in the associated LP, while blue ones are down-regulated, and grey ones are related to more than one phenotypes with alternate up-down regulations (details of the full network in Suppl. Table 2). Orderedlist parameter T=200 (Methods).

Evaluation A  87 samples 48 Epigenetic Seed Genes

Random 3-folds Significant  Ross et. al. similar? (http://www. ESG Outcome stjuderesearc EpigeNet h.org/data/) 58 samples’ outcome 7,256 gene’s Genes co-Expressed with expression Mechanism genes (GEMs) profiles Expression profiles of identified ESGs + GEMs SVM machine learning (linear model) SupportVectors 29 samples’ outcome Classification based on SVM predicted model Repeat 100 times Outcome Predictions (a) Evaluation B  87 samples 48 Epigenetic Seed Genes

Random 3-folds Significant similar? ESG Outcome

7,256 gene’s 58 samples’ outcome EpigeNet expression profiles Genes co-Expressed with Mechanism genes (GEMs)

Expression profiles of identified ESGs + GEMs 29 samples’ outcome Classification based on PAM (no machine learning)

Repeat 100 times Outcome Predictions

(b)

Supplementary Figure 2. The Design of the Evaluations. The 87 leukemia patients with “CCR” or “relapse” information were randomly divided into three stratified folds, two of which were used to identify the relapse associated GEMs and ESGs, and the remaining one third of samples was used as a blinded test set. Such 3-fold cross-validation (the processes in the dash box) was repeated 100 times. Panel (a) shows the evaluation with machine-learning while panel (b) without machine learning. Result from Evaluation A was shown in Fig. 3 in the main document and in Suppl. Fig. 4 and the result from Evaluation B was shown in Suppl. Fig. 3. AUC=0.65 P=0.03

1-specificity (CCR) Supplementary Figure 3. The ROC curve of the computational evaluation method B of PGnet-predicted GEMs and ESGs signature associated with ALL relapse. Computational evaluation method B of PGnet-predicted GEMs and ESGs signature associated with ALL relapse. The 87 leukemia patients with “CCR” or “relapse” information were randomly divided into three stratified folds, two of which were used to identify the outcome (“CCR” vs. “relapse”) associated GEMs and ESGs, and the remaining one was used as a blinded test set using PAM. Such three-fold cross-validation was repeated 100 times. The resulting ROC curve, area under the curve and corresponding p-values were calculated by Bioconductor package verification.

Supplementary Figure 4. The precision_recall results of the computational evaluation A of PGnet-predicted GEMs and ESGs signature associated with ALL relapse. The 87 leukemia patients with “CCR” or “relapse” information were randomly divided into three folds, two of which were used to identify the outcome (“CCR” vs. “relapse”) associated GEMs and ESGs to train a linear SVM model, and the remaining one was used as a blinded test set. Such three-fold cross-validation was repeated 100 times. The left panel is the correspondind precision-recall graph; while the right panel is the box-and-whisker plot (the smallest observation = circle, the lower quartile, median and upper quartile, and the largest observation, whiskers are the 95% and 5% intervals) showing outliers as single points for the precisions and recalls.

Supplementary Figure 5. Expression pattern of ALL phenotype “Hyperdiploid>50” specific and co-expressed with known ESGs genes (GEMs) by PGnet. Four ESGs were associated to this pattern as shown in Figure 2 in the main document. Supplementary Table 1

The eight categories of epigenetic key terms and their corresponding 71 epigenetic seed genes

Biological Function or Queried Biological Process related to or Genes/Gene family Associated Genes targeted by Epigenetic (Term used in Regulation Pubmed) MBD1,2 MBD1 MBD2 MBD3 MBD4 MBD5 Methyl-binding ▲ 1 protein MECP2 MECP2 ZBTB333,4 ZBTB33 DNA DNMT2,5 DNMT1 DNMT3A DNMT3B DNMT3L ▲ Methyltransferase Histon histone HAT1 MYST1 MYST2 MYST3 MYST4 ▲ acetyltransferase acetyltransferase6,7 DOT1L6 DOT1L Histone deacetylase ▲ HDAC2,8 HDAC1 HDAC11 HDAC2 HDAC3 HDAC4 HDAC5 HDAC6 HDAC7A HDAC9 SETDB1,9 SETDB1 SUV39H10,11 SUV39H1 SUV39H2 ash112 ASH1L Histone PRDM10,13,14 PRDM10 PRDM11 PRDM12 PRDM13 PRDM14 ▲ methyltransferase PRDM2 PRDM4 PRDM5 PRDM8 PRDM9 PRDM16 SMYD315 SMYD3 EHMT10,16 EHMT1 EHMT2 Histone modificated CBX11,17 CBX111 CBX2 CBX3 CBX4 CBX5 ▲ chromobox protein CBX6 CBX7 CBX8 ▲ Imprinting ** KCNQ1 IGF2 PHLDA2 CTCF DIRAS3 BAZ218 BAZ2A BAZ2B Chromatin SMARC19,20 SMARCA1 SMARCA2 SMARCA4 SMARCA5 SMARCAL1 ▲ remodeling SMARCB1 SMARCC1 SMARCC2 SMARCD1 SMARCD2 SMARCD3 SMARCE1 Terms with quotation marks are used for gene name searching, ** were searched by GO group “imprinting” using “GO:0006349”. Forty-eight epigenetic seed genes (ESGs) with bold-face passed our IQR filtering. The second column gives the terms to be mapped; the third column lists the official gene symbols.

References: 1. Roloff TC, Ropers HH, Nuber UA. Comparative study of methyl-CpG-binding domain proteins. BMC Genomics. 2003 Jan 16;4(1):1. 2. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer. 2004 Feb;4(2):143-53. Suppl. Table 1 – page 1

3. Kim SW, Park JI, Spring CM, et al. Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol. 2004 Dec;6(12):1212-20. 4. Filion GJ, Zhenilo S, Salozhin S, Yamada D, Prokhortchouk E, Defossez PA. A family of human zinc finger proteins that bind methylated DNA and repress transcription. Mol Cell Biol. 2006 Jan;26(1):169-81. 5. Hermann A, Gowher H, Jeltsch A. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci. 2004 Oct;61(19-20):2571-87. 6. McManus KJ, Hendzel MJ. Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol. 2003 Nov;23(21):7611-27. 7. Georgiakaki M, Chabbert-Buffet N, Dasen B, et al. Ligand-controlled interaction of histone acetyltransferase binding to ORC-1 (HBO1) with the N-terminal transactivating domain of progesterone receptor induces steroid receptor coactivator 1-dependent coactivation of transcription. Mol Endocrinol. 2006 Sep;20(9):2122-40. 8. Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia. 2005 Oct;19(10):1751-9. 9. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ, 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002 Apr 15;16(8):919-32. 10. Kim KC, Geng L, Huang S. Inactivation of a histone methyltransferase by mutations in human cancers. Cancer Res. 2003 Nov 15;63(22):7619-23. 11. Garcia-Cao M, O'Sullivan R, Peters AH, Jenuwein T, Blasco MA. Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet. 2004 Jan;36(1):94-9. 12. Gregory GD, Vakoc CR, Rozovskaia T, et al. Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol Cell Biol. 2007 Dec;27(24):8466-79. 13. Reid AG, Nacheva EP. A potential role for PRDM12 in the pathogenesis of chronic myeloid leukaemia with derivative chromosome 9 deletion. Leukemia. 2004 Jan;18(1):178-80. 14. Pastural E, Takahashi N, Dong WF, et al. RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines. Oncogene. 2007 Mar 8;26(11):1586-94. 15. Hamamoto R, Furukawa Y, Morita M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004 Aug;6(8):731-40. 16. Pless O, Kowenz-Leutz E, Knoblich M, et al. G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta. J Biol Chem. 2008 Sep 26;283(39):26357-63. 17. Bernstein E, Duncan EM, Masui O, Gil J, Heard E, Allis CD. Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin. Mol Cell Biol. 2006 Apr;26(7):2560-9. 18. Zhou Y, Santoro R, Grummt I. The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J. 2002 Sep 2;21(17):4632-40.

Suppl. Table 1 – page 2

19. Moinova HR, Chen WD, Shen L, et al. HLTF gene silencing in human colon cancer. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4562-7. 20. Pottier N, Yang W, Assem M, et al. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst. 2008 Dec 17;100(24):1792-803.

Suppl. Table 1 – page 3

Supplementary Table 2

Thirty-three significant “LP-ESG” linkages and their corresponding GEMs (orderedlist parameter T=200)

LP: Leukemia Phenotype ESG: Epigenetic Seed Gene P: The un-adjusted empirical vectorial enrichment p-value of every significant (p<0.001) “LP-ESG” pair Dir: “+” represents straight similar, “-” represents reversed similar ESG.dys: The average change of ESGs in expression to its linked leukemia phenotype compared to other phenotypes. Opt.T: The optimal parameter T which achieves lowest empirical p for a given range of T candidates (100, 150, 200, 300, 400, 500, 750, 1000, 2000, 2500) based on 1000 random permutations of vectors. O(T): The counts of Genes co-Expressed with Mechanism genes (GEMs) using the corresponding optimal parameter T. O(200): The counts of GEMs using a parameter T=200. GEMs(200): The predicted GEMs using a parameter T=200.

LP ESG P Dir ESG.dys Opt.T O(T) O(200) GEMs(200) SPIN2B; ADFP; FAM45B; TMEM164; TCEAL1; HNRPH2; PIN4; PCDH9; Pseudodip BAZ2A <0.001 + up 300 15 9 dJ222E13.2 ADK; PTGES3; C22orf9; KIAA0564; ITM2C; C11orf24; ANXA2; PKIG; VGLL4; VAV1; KNTC1; SMAD1; RASA4; SCARB1; GNG11; RY1; CBFA2T3; PDLIM7; TNFRSF21; ABHD3; LOC654342; TCFL5; TNS1; TEL-AML1 DNMT3A <0.001 + up 200 25 25 C10orf26; ARHGEF4 CD74; HLA-DRA; HLA-DRB1; CD19; BLNK; HLA-DPA1; C14orf139; HLA-DPB1; HLA-DRB5; TCL1A; CD79A; POU2AF1; TFEB; CHD7; CTNNA1; HLA-DQB1; SLC27A3; PTPN18; BANK1; STX3; HLA-DRB6; PFTK1; CD9; PTK2; TRIM38; ENG; FHL1; STK32B; DSTN; ZNF167; SEMA4D; AGL; C9orf78; ATP1B1; C14orf135; LZTFL1; NUCB2; SHQ1; T-ALL DNMT3B <0.001 + up 100 15 40 WDR67; TRD@ CD74; HLA-DRA; HLA-DRB1; BLNK; HLA-DPA1; HLA-DPB1; HLA- DMA; HLA-DRB5; CD79B; MEF2C; TCL1A; CD79A; SNX2; JUP; POU2AF1; TFEB; CHD7; GALNAC4S-6ST; HLA-DQB1; LAMC1; STX7; SLC27A3; PTPN18; HLA-DMB; BANK1; HLA-DRB6; PTK2; ENG; tcag7.1314; HLA-F; FHL1; STK32B; SLC25A15; INSIG1; DSTN; HIRA; ZAP70; NOTCH3; MLLT11; C9orf78; VAT1; PELO; C14orf135; LZTFL1; CD247; NUCB2; PEX5; CHI3L2; NBR1; USP20; LAT; BCL11B; LCK; T-ALL HDAC4 <0.001 + up 100 19 56 UBASH3A; MAL; CD3D MGC29506; MME; MYO5C; SERPINB9; MYH10; FHIT; COL5A1; DPEP1; MLL HDAC9 <0.001 + up 100 23 51 PARD3; SMAD1; VAMP5; HYI; GFOD1; ALOX5; POLE; NEDD4;

Suppl. Table 2 – page 1

LP ESG P Dir ESG.dys Opt.T O(T) O(200) GEMs(200)

SCHIP1; MDK; STK32B; GIMAP4; DDR1; MYO1B; FGD1; EDEM1; PTP4A3; ADK; PTGES3; TPP2; GLT8D1; STS; ADAM10; C22orf9; GALC; ZEB2; IGFBP7; LY75; WIPI1; CD72; SIDT2; HK2; C11orf24; CD44; FEZ2; FAIM; NLRP3; MPZL1; PLXNC1; ATP8B4; LGALS1; KLRK1; C20orf103 RAG2; ABCC4; AKAP12; PQBP1; ARMCX5; CXorf45; UBE2A; ABCD4; ATP6AP2; MAGEH1; LAS1L; RRP1B; GPKOW; MORC3; HNRPH2; ABCB7; UBQLN2; SLC9A6; FTSJ1; USP9X; RNF113A; MED12; RP6- Hyperdip>50 HDAC6 <0.001 + up 300 41 25 213H19.1; PSMD10; UPF3B MGC29506; MYH10; DPEP1; AKAP12; PARD3; ITPR3; MAGED1; EMP2; STAT4; RASA1; PABPC4; MED13L; SMARCA2; ZNF394; SIRT7; TSEN34; SH3YL1; ARL6IP5; MAN2B1; ZEB2; OXA1L; LY75; AK2; MLL SMARCA2 <0.001 + up 300 60 31 CDKN1B; FUT4; C1orf164; FEZ2; PCDHGC3; DAD1; PLXNC1; IGF2BP2 CD74; HLA-DRA; HLA-DRB1; HLA-DPA1; HLA-DPB1; HLA-DMA; HLA-DRB5; CD79B; CD24; TCL1A; CD79A; POU2AF1; CHD7; HLA- T-ALL SMYD3 <0.001 + up 100 10 17 DQB1; SLC27A3; HLA-DRB6; tcag7.1314 EVI2A; SOCS2; CCND2; PLSCR1; ARHGAP4; GUSB; LTB4R; HPCAL1; TMEM134; XBP1; TUSC4; SH3BP4; RHOBTB1; SLC15A2; FNDC3B; CALD1; APBB2; EAF2; PLEKHF2; ELL3; ROR1; ADARB1; DACT1; KCNJ12; GOLGA3; FHOD3; SEMA4C; GP5; HIP1R; NID2; KIAA0802; E2A-PBX1 PHLDA2 <0.001 + up 200 34 34 SYNPO; SLC27A2; PBX1 Relapse HDAC9 <0.001 + up 400 10 5 MYH10; SALL2; CEBPE; LGALS1; IGFBP7 FAM120A; MBD2; MRCL3; DSC2; DUOX1; ANGPTL2; DLGAP2; SEMA3F; DRAM; PTPRK; KCNK3; GBA3; TMEM16A; LOC654342; TEL-AML1 MBD2 <0.001 - down 300 47 20 NOVA1; HAP1; FBN2; PCLO; BIRC7; ARHGEF4 ELF1; ZNF75; ARMCX5; ASB9; ENOX2; UBE2A; ATP6AP2; MGC39900; MORC3; HNRPH2; PRKAR2B; WDR44; SOD1; SLC9A6; SETD3; FTSJ1; ARMCX1; MTCP1; PIGP; LOC57228; DHRS4; RP6-213H19.1; CRYZL1; Hyperdip>50 BAZ2A <0.001 - down 150 21 27 PSMD10; TCEAL1; TCEAL4; UPF3B GNAQ; PRKACB; KIAA0430; SNAP23; AKAP11; STX16; GNPTAB; HSD17B11; TTC31; SLC35E2; LETMD1; F13A1; LTBP2; DOCK9; PSAT1; ODZ4; QRSL1; GNAZ; KCNA3; TMEM121; RASAL1; ELOVL2; CCDC81; IL12RB2; IGSF3; KCNMB3; ELL3; IRF4; ROR1; SAMD4A; KCNJ12; FAT; NCAPD3; FHOD3; SORBS1; SEMA4C; GP5; HIP1R; NID2; PRKCZ; E2A-PBX1 BAZ2B <0.001 - down 100 25 45 KIAA0802; SYNPO; PSEN2; MERTK; PBX1 ZMYND11; CTDSP2; ARHGAP4; SLC35E2; STAT5B; EXOC1; ARNTL2; MAP3K1; MAP1B; FGF9; GPR176; ENDOD1; SYT1; CCDC81; IL12RB2; APBB2; EAF2; KCNMB3; BLK; IRF4; AOX1; ROR1; SAMD4A; LRMP; KANK1; DACT1; FHOD3; SLAMF1; GP5; SYNPO; PSEN2; SLC27A2; E2A-PBX1 MECP2 <0.001 - down 150 22 33 PBX1

Suppl. Table 2 - page 2

LP ESG P Dir ESG.dys Opt.T O(T) O(200) GEMs(200)

C5orf13; GLUL; JARID1B; MVP; STX3; GIMAP4; S100A13; MS4A1; BCR-ABL DNMT3B <0.001 - down 300 30 12 RAPGEF3; TBXA2R; ENG; ECM1 PAX5; C14orf139; MEF2C; BTK; SNX2; JUP; PLCG2; CIITA; NCF4; TFEB; IGHM; CTNNA1; MSRA; HLX; LAPTM5; NUBP1; PLXNB2; ROGDI; MARCH3; SIPA1; LRP10; ST18; ZNF167; LIMA1; RGS10; SNX10; SLC19A2; ITM2A; CMAH; ATP1B1; PTPN22; CD2; GATA3; FXYD2; AKR1C3; GALNT6; NGFRAP1; STAU2; ITK; DENND2D; CHI3L2; CD28; TFDP2; AQP3; IL23A; PTPN7; BIN2; LAT; BCL11B; PRKCQ; LCK; SCD; CD7; TRAT1; UBASH3A; CD3E; TRD@; MAL; T-ALL HDAC5 <0.001 - down 100 25 60 SH2D1A; CD3D GLUL; PKIA; TUSC4; HDAC4; ITGAE; GIMAP4; PALM; FLJ20489; BCR-ABL HDAC4 <0.001 - down 300 28 15 CCND2; S100A13; P2RY14; RAPGEF3; ENG; ECM1; SLC2A5 ADK; PTGES3; SORD; IQGAP2; C22orf9; PUS7; CD44; PTGER4; MINA; ATP8A1; C11orf24; MPZL1; FLJ11184; FAM98A; CTSC; FXN; EDEM1; GABBR1; CD27; ZNF91; AJAP1; SMAD1; FARP1; FERMT2; SEMA6A; SH3GLB2; H1F0; GNG11; SPTA1; DSG2; MDK; PTP4A3; RAG1; NRN1; TSPYL5; TERF2; NR3C2; SPANXA1; KCNK3; TUSC3; ARHGAP29; TEL-AML1 HDAC9 <0.001 - down 100 15 47 TNFRSF21; LOC654342; NOVA1; HAP1; PCLO; ARHGEF4 IGFBP7; LGALS1; WIPI1; ATP8B4; TBK1; NLRP3; MYO1F; PTGES3; CCR HDAC9 <0.001 - down 200 13 13 HK2; FEZ2; POLE; NUDT11; SALL2 GNAQ; CD99; CTDSP2; LASP1; ITGB1; PRKCB1; AMZ2; STX16; GPSM3; SLC35E2; DGAT1; C14orf1; TMC6; TMEM134; F13A1; GALNT14; SYT1; RASAL1; APBB2; EAF2; ELL3; BLK; IRF4; AOX1; ROR1; SAMD4A; LRMP; KANK1; DACT1; NP; FHOD3; SLAMF1; GP5; E2A-PBX1 HDAC7 <0.001 - down 100 20 38 PRKCZ; SYNPO; PSEN2; MERTK; PBX1 HMHA1; TM9SF3; SNAP23; AKAP11; JMJD1C; HSD17B11; CNDP2; METTL7A; LETMD1; NFATC3; EXOC1; EMP2; MAGED1; ARNTL2; LTBP2; DOCK9; CASC1; PSAT1; KCNA3; ALDH1A1; ELOVL2; ROR1; E2A-PBX1 SMARCA2 <0.001 - down 300 49 30 FAT; FHOD3; SLAMF1; HIP1R; NID2; PRKCZ; PSEN2; PBX1 COMMD4; ANP32A; BCL2L1; SMARCA4; SPTBN1; PSME4; HDGF; TLR2; ECHDC3; IL6R; ALDH3B1; ITSN1; MS4A6A; PLP2; IL13RA1; Hyperdip>50 SMARCA4 <0.001 - down 200 17 17 IL3RA; ZNF185 KIAA0101; TYMS; HMGN2; SMS; RBBP7; UCHL5IP; UBE2A; CDC2; TBC1D25; SOD1; CBLB; DLGAP4; CD84; ZNF192; CSHL1; ITGA6; Normal SUV39H1 <0.001 - down 300 39 23 FLT1; PCDH9; AGMAT; MPPED2; HEY2; LHFPL2; STAP1 SHCBP1; NCAPH; TOP2A; ARHGAP19; KIF4A; SPAG5; CCNB2; CDC45L; C21orf45; BIRC5; KIF11; PLK4; TIMELESS; MAD2L1; AURKB; Relapse SUV39H1 <0.001 - down 200 22 22 KIF2C; H2AFZ; CKS1B; ZWINT; RAD51; NPR3; FLJ13197 CD24; CD79A; POU2AF1; INSR; CUL1; GNG7; AUTS2; TRAK1; MLXIP; T-ALL PRDM2 <0.001 - down 200 30 30 PCBP3; SLC9A3R1; FAH; LIME1; PELO; EPHB6; PEX5; GATA3; FXYD2;

Suppl. Table 2 - page 3

LP ESG P Dir ESG.dys Opt.T O(T) O(200) GEMs(200)

AKR1C3; GALNT6; NGFRAP1; TFDP2; AQP3; LAT; TRAT1; UBASH3A; CD3E; MAL; SH2D1A; CD3D PKIA; HDAC4; RABL4; SERPINB6; GIMAP4; PALM; HPCAL1; FLJ20489; ITGA5; CCND2; S100A13; P2RY14; RAPGEF3; ARHGEF17; TBXA2R; ASB13; LIMD1; BAALC; PRX; ENG; TBX21; ECM1; SLC2A5; BCR-ABL CBX1 <0.001 - down 100 8 25 LOC26010; OLFML2A CIRBP; CTDSP2; ARHGAP4; SAPS2; DGAT1; TMEM134; CASC1; SLC15A2; ALDH1A1; RASAL1; CCDC81; APBB2; EAF2; SAMD4A; E2A-PBX1 CBX6 <0.001 - down 200 21 21 KANK1; DACT1; GP5; SYNPO; PSEN2; SLC27A2; PBX1 NUCKS1; KIAA0101; TYMS; SS18L2; CDC2; PTTG1; FH; TP53TG3; Normal CBX5 <0.001 - down 300 35 16 CCR5; CSHL1; REEP1; FLT1; FER1L3; SLC6A16; AGMAT; GFOD1 TUBB; NCAPH; TOP2A; MKI67; TPX2; ANP32E; KIF20A; CCNB2; BUB1; CCNA2; AURKB; KIF2C; H2AFZ; CKS1B; ZWINT; NPR3; Relapse CBX5 <0.001 - down 100 9 17 FLJ13197 Hyperdip>50 CBX7 0.004 - down 400 26 7 ECHDC3; ITSN1; MYBPC2; C10orf56; IL13RA1; IL3RA; ZNF185 TMED10; MORC3; SEL1L; EMP2; PRR5; PPFIA4; ARNTL2; SGSM3; EWSR1; GPR176; ODZ4; QRSL1; GNAZ; ALDH1A1; RASAL1; KCNMB3; ROR1; DACT1; KCNJ12; FAT; NID2; PRKCZ; SYNPO; PSEN2; MERTK; E2A-PBX1 MYST2 <0.001 - down 300 43 26 PBX1 ZMYND11; ARNTL2; GPR176; PSAT1; QRSL1; TMEM121; RASAL1; CCDC81; KCNMB3; IRF4; AOX1; ROR1; SAMD4A; DACT1; SLAMF1; E2A-PBX1 MYST4 <0.001 - down 100 10 19 NID2; SYNPO; PSEN2; PBX1 Relapse DNMT3A <0.001 - down 750 23 6 DBN1; TUBB; SEPHS1; ZNF675; PRPF4B; S100A4

Suppl. Table 2 - page 4

Supplementary Table 3

The predicted GEMs of 117 significant “LP-ESG” linkages based on optimal Ts

--- 102 linkages with p-value smaller than 0.02 were estimated to be none-false discovery (Suppl. Methods)

LP: Leukemia Phenotype ESG: Epigenetic Seed Gene p: The un-adjusted empirical vectorial enrichment p-value of every significant (p<0.001) “LP-ESG” pair q: The estimated false discovery rate (proportion of false positives incurred) at given empirical p-value threshold. Dir: “+” represents straight similar, “-” represents reversed-similar ESG.dys: The average change of ESGs in expression to its linked leukemia phenotype compared to other phenotypes. Opt.T: The optimal parameter T which achieves lowest empirical p for a given range of T candidates (100, 150, 200, 300, 400, 500, 750, 1000, 2000, 2500) based on 1000 random permutations of vectors. O(T): The counts of Genes co-Expressed with Mechanism genes (GEMs) using the corresponding optimal parameter T. GEMs(T): The predicted GEMs using the corresponding optimal parameter T.

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T) SPIN2B; ALG13; ADFP; RP2; ARFIP1; FAM45B; TMEM164; LAMP2; Pseudodip BAZ2A <0.001 0 + up 300 15 TCEAL1; HNRPH2; PIN4; GLT25D1; SH2B2; PCDH9; dJ222E13.2 ADK; PTGES3; C22orf9; KIAA0564; ITM2C; C11orf24; ANXA2; PKIG; VGLL4; VAV1; KNTC1; SMAD1; RASA4; SCARB1; GNG11; RY1; CBFA2T3; PDLIM7; TNFRSF21; ABHD3; LOC654342; TCFL5; TNS1; C10orf26; TEL-AML1 DNMT3A <0.001 0 + up 200 25 ARHGEF4 CD74; HLA-DRA; HLA-DRB1; BLNK; HLA-DPA1; HLA-DPB1; HLA-DRB5; T-ALL DNMT3B <0.001 0 + up 100 15 TCL1A; TFEB; CTNNA1; HLA-DQB1; SLC27A3; NUCB2; SHQ1; WDR67 CD74; HLA-DRA; HLA-DRB1; BLNK; HLA-DPA1; HLA-DPB1; HLA-DMA; HLA-DRB5; JUP; CHD7; HLA-DQB1; STX7; SLC27A3; NUCB2; CHI3L2; T-ALL HDAC4 <0.001 0 + up 100 19 LAT; BCL11B; LCK; MAL MGC29506; MME; MYH10; FHIT; COL5A1; DPEP1; PARD3; SMAD1; VAMP5; HYI; GFOD1; ALOX5; POLE; SCHIP1; WIPI1; HK2; C11orf24; MLL HDAC9 <0.001 0 + up 100 23 FEZ2; FAIM; NLRP3; PLXNC1; LGALS1; C20orf103 OR7E38P; RAG2; ABCC4; TPD52; AKAP12; MCTP2; PCDH9; TTC3; PDHA1; SH3BGRL; HDAC6; CETN2; STAG2; HUWE1; TMEM164; PHKA2; CUL4B; Hyperdip>5 PQBP1; ARMCX5; CXorf45; UBE2A; ABCD4; ATP6AP2; MAGEH1; LAS1L; 0 HDAC6 <0.001 0 + up 300 41 RRP1B; GPKOW; MORC3; HNRPH2; ABCB7; UBQLN2; SLC9A6; FTSJ1;

Suppl. Table 3 – page 1 LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

USP9X; RNF113A; MED12; RP6-213H19.1; CRYZL1; PSMD10; TCEAL1; UPF3B MGC29506; MME; CD52; EXDL2; MYH10; DPEP1; AKAP12; PARD3; ITPR3; MAGED1; HYI; DBN1; EMP2; FGD1; BMPR2; STAT4; ZNF415; SALL2; ZNF667; ODZ4; TREML2; SPAG16; RAPGEF3; COPS7A; RNFT1; DVL1; EP400; PHF6; MYH9; RPS6KA1; IKBKB; PLXNB2; JMJD1C; RASA1; PABPC4; MED13L; SMARCA2; ZNF394; COQ2; MAP4; RPP40; SIRT7; TSEN34; SH3YL1; ARL6IP5; MAN2B1; ZEB2; OXA1L; LY75; AK2; CDKN1B; FUT4; C1orf164; ADCY9; FEZ2; FAIM; PCDHGC3; DAD1; MLL SMARCA2 <0.001 0 + up 300 60 PLXNC1; IGF2BP2 CD74; HLA-DRA; HLA-DRB1; HLA-DPA1; HLA-DPB1; HLA-DMA; HLA- T-ALL SMYD3 <0.001 0 + up 100 10 DRB5; TCL1A; POU2AF1; SLC27A3 EVI2A; SOCS2; CCND2; PLSCR1; ARHGAP4; GUSB; LTB4R; HPCAL1; TMEM134; XBP1; TUSC4; SH3BP4; RHOBTB1; SLC15A2; FNDC3B; CALD1; APBB2; EAF2; PLEKHF2; ELL3; ROR1; ADARB1; DACT1; KCNJ12; GOLGA3; FHOD3; SEMA4C; GP5; HIP1R; NID2; KIAA0802; SYNPO; E2A-PBX1 PHLDA2 <0.001 0 + up 200 34 SLC27A2; PBX1 DBN1; HMGB3; MYH10; SALL2; CEBPE; LGALS1; IGFBP7; MFSD1; Relapse HDAC9 <0.001 0 + up 400 10 S100A4; AHR NME2; FAM120A; CCDC28A; VIM; MBD2; MRCL3; ACAT2; FDX1; ME2; SRP72; ARHGAP24; NOL4; PRO2268; GPR17; DSC2; DUOX1; CACNB2; SPON1; MSR1; AJAP1; FERMT2; EHD2; TFPI; ANGPTL2; DLGAP2; MAPK13; MDK; TRPM4; SEMA3F; CXCR7; DRAM; PTPRK; MYO10; SPANXA1; KCNK3; TUSC3; GBA3; TMEM16A; LOC654342; NOVA1; HAP1; TEL-AML1 MBD2 <0.001 0 - down 300 47 FBN2; TNS1; PCLO; BIRC7; CLIC5; ARHGEF4 ATP6AP2; MGC39900; MORC3; HNRPH2; PRKAR2B; WDR44; SOD1; Hyperdip>5 SLC9A6; SETD3; FTSJ1; ARMCX1; MTCP1; PIGP; LOC57228; DHRS4; RP6- 0 BAZ2A <0.001 0 - down 150 21 213H19.1; CRYZL1; PSMD10; TCEAL1; TCEAL4; UPF3B GNAQ; PRKACB; AKAP11; STX16; GNPTAB; TMEM121; RASAL1; ELOVL2; CCDC81; IL12RB2; IGSF3; KCNMB3; ELL3; IRF4; ROR1; SAMD4A; E2A-PBX1 BAZ2B <0.001 0 - down 100 25 KCNJ12; FAT; FHOD3; HIP1R; NID2; PRKCZ; SYNPO; MERTK; PBX1 CTDSP2; ARHGAP4; SLC35E2; MAP1B; SYT1; CCDC81; IL12RB2; APBB2; EAF2; BLK; IRF4; AOX1; ROR1; SAMD4A; KANK1; DACT1; FHOD3; E2A-PBX1 MECP2 <0.001 0 - down 150 22 SLAMF1; GP5; SYNPO; PSEN2; PBX1 C5orf13; GLUL; ITGAE; JARID1B; HK2; IGFBP4; MYO5C; PTPN18; NAV1; SLC35D2; SCHIP1; SCN1B; CAST; MVP; STX3; GIMAP4; HPCAL1; MTSS1; SH2B3; S100A13; TNFRSF1B; MS4A1; RAPGEF3; EMP1; TBXA2R; SEMA6A; BCR-ABL DNMT3B <0.001 0 - down 300 30 ENG; TBX21; ECM1; OLFML2A PAX5; C14orf139; MEF2C; BTK; CIITA; NCF4; TFEB; IGHM; CTNNA1; T-ALL HDAC5 <0.001 0 - down 100 25 GATA3; FXYD2; NGFRAP1; ITK; TFDP2; AQP3; IL23A; PTPN7; CD7;

Suppl. Table 3 – page 2

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

TRAT1; UBASH3A; CD3E; TRD@; MAL; SH2D1A; CD3D GLUL; PKIA; TUSC4; HDAC4; ITGAE; MYO5C; PTPN18; NAV1; SLC35D2; SCHIP1; LUZP1; DUSP6; SERPINB6; STX3; GIMAP4; PALM; FLJ20489; CCND2; S100A13; OSBPL10; P2RY14; RAPGEF3; SEMA6A; LIMD1; ENG; BCR-ABL HDAC4 <0.001 0 - down 300 28 ECM1; SLC2A5; OLFML2A ADK; PTGES3; IQGAP2; C22orf9; PUS7; MINA; ATP8A1; C11orf24; DSG2; TEL-AML1 HDAC9 <0.001 0 - down 100 15 PTP4A3; TSPYL5; TERF2; TUSC3; ARHGAP29; TNFRSF21 IGFBP7; LGALS1; WIPI1; ATP8B4; TBK1; NLRP3; MYO1F; PTGES3; HK2; CCR HDAC9 <0.001 0 - down 200 13 FEZ2; POLE; NUDT11; SALL2 CD99; CTDSP2; LASP1; ITGB1; SYT1; APBB2; EAF2; ELL3; BLK; IRF4; SAMD4A; LRMP; KANK1; DACT1; NP; FHOD3; GP5; SYNPO; PSEN2; E2A-PBX1 HDAC7 <0.001 0 - down 100 20 PBX1 HMHA1; SNX3; TM9SF3; SNAP23; AKAP11; JMJD1C; GALNT1; RALB; HSD17B11; CNDP2; METTL7A; LETMD1; NFATC3; RNF13; UBE4A; EXOC1; TMEM30A; B3GNT2; OS9; TMEM43; ARHGEF11; MYT1L; MYL4; PAWR; ARL4C; EMP2; MAGED1; ARNTL2; LTBP2; DOCK9; CASC1; PSAT1; ODZ4; D4S234E; KCNA3; ALDH1A1; KIAA0922; ELOVL2; ROR1; FAT; FHOD3; E2A-PBX1 SMARCA2 <0.001 0 - down 300 49 SLAMF1; GP5; HIP1R; NID2; PRKCZ; PSEN2; MERTK; PBX1 COMMD4; ANP32A; BCL2L1; SMARCA4; SPTBN1; PSME4; HDGF; TLR2; Hyperdip>5 ECHDC3; IL6R; ALDH3B1; ITSN1; MS4A6A; PLP2; IL13RA1; IL3RA; 0 SMARCA4 <0.001 0 - down 200 17 ZNF185 APITD1; TRMT5; KIAA0101; TYMS; LAGE3; HMGN2; SMS; RBBP7; UCHL5IP; UBE2A; CDC2; TBC1D25; ATP5J; HMGN1; SOD1; CCNB2; MCM6; SLC25A5; EIF4A3; EBP; H2AFZ; TOP2A; PSMG1; CKS1B; C4orf27; CBLB; DLGAP4; CD84; ZNF192; CSHL1; ITGA6; FLT1; PCDH9; FER1L3; Normal SUV39H1 <0.001 0 - down 300 39 AGMAT; MPPED2; HEY2; LHFPL2; STAP1 SHCBP1; NCAPH; TOP2A; ARHGAP19; KIF4A; SPAG5; CCNB2; CDC45L; C21orf45; BIRC5; KIF11; PLK4; TIMELESS; MAD2L1; AURKB; KIF2C; Relapse SUV39H1 <0.001 0 - down 200 22 H2AFZ; CKS1B; ZWINT; RAD51; NPR3; FLJ13197 CD24; CD79A; POU2AF1; INSR; CUL1; GNG7; AUTS2; TRAK1; MLXIP; PCBP3; SLC9A3R1; FAH; LIME1; PELO; EPHB6; PEX5; GATA3; FXYD2; AKR1C3; GALNT6; NGFRAP1; TFDP2; AQP3; LAT; TRAT1; UBASH3A; T-ALL PRDM2 <0.001 0 - down 200 30 CD3E; MAL; SH2D1A; CD3D BCR-ABL CBX1 <0.001 0 - down 100 8 PKIA; HDAC4; TBXA2R; LIMD1; ENG; ECM1; SLC2A5; OLFML2A CIRBP; CTDSP2; ARHGAP4; SAPS2; DGAT1; TMEM134; CASC1; SLC15A2; ALDH1A1; RASAL1; CCDC81; APBB2; EAF2; SAMD4A; KANK1; DACT1; E2A-PBX1 CBX6 <0.001 0 - down 200 21 GP5; SYNPO; PSEN2; SLC27A2; PBX1 NUCKS1; KIAA0101; TYMS; SS18L2; CDC2; PTTG1; FH; CCNB2; TUBA1C; Normal CBX5 <0.001 0 - down 300 35 MCM6; RPA3; RFC4; KIF18A; H2AFZ; NDUFA6; CBX5; TOP2A; NDUFS6;

Suppl. Table 3 – page 3

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

CKS1B; RAN; SFRS2B; TUBB2C; AMT; TP53TG3; CCR5; EFR3B; PRKG2; ZNF239; CSHL1; REEP1; FLT1; FER1L3; SLC6A16; AGMAT; GFOD1 Relapse CBX5 <0.001 0 - down 100 9 TUBB; NCAPH; MKI67; TPX2; KIF20A; CCNB2; BUB1; NPR3; FLJ13197 TTC15; ADAM17; SENP7; USP4; DLEU2L; MPHOSPH8; MZF1; REPIN1; ARID4B; VEGFB; POLA1; PET112L; RRP1; PRKAR2B; ECHDC3; IL6R; Hyperdip>5 CYB5A; SETD3; ALDH3B1; ITSN1; MYBPC2; PLP2; C10orf56; IL13RA1; 0 CBX7 0.004 0.04189 - down 400 26 IL3RA; ZNF185 MSN; TMED10; MORC3; SEL1L; TMEM30A; ZFP106; CLINT1; ATP6AP2; YPEL1; TCF3; MYL4; JAG1; JAM2; KCNJ16; EPB41L2; EMP2; PRR5; PPFIA4; ARNTL2; PHACTR1; SGSM3; EWSR1; GPR176; ODZ4; QRSL1; GNAZ; ALDH1A1; CALD1; RASAL1; KCNMB3; ROR1; DACT1; KCNJ12; FAT; SLAMF1; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; MERTK; E2A-PBX1 MYST2 <0.001 0 - down 300 43 PBX1 RASAL1; KCNMB3; IRF4; AOX1; ROR1; SAMD4A; DACT1; SLAMF1; E2A-PBX1 MYST4 <0.001 0 - down 100 10 SYNPO; PSEN2 DBN1; MCM10; TUBB; HMGB3; SEPHS1; HRB; TIMELESS; ZNF675; PRPF4B; C11orf21; LGALS1; IGFBP7; S100A4; P2RX5; NPR3; DKFZp686O1327; PSTPIP2; FOXP1; AHR; PLCB1; FLJ13197; CCPG1; Relapse DNMT3A <0.001 0 - down 750 23 TSPAN32 CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; BTK; CD79A; SNX2; VPREB3; JUP; PLCG2; CIITA; NCF4; POU2AF1; TFEB; IGHM; CHD7; GALNAC4S-6ST; CTNNA1; RIPK2; TCF4; HLA-DQB1; MSRA; INSR; HLX; LAMC1; INPP5D; STX7; SLC27A3; EGLN1; LAPTM5; LAT2; HLA-DMB; BANK1; TSPAN13; STX3; HLA-DRB6; PFTK1; CD9; CD22; PTPRE; BACH2; HCP5; GNG7; AUTS2; PTK2; RHBDF2; LILRA6; LILRA2; TRIM38; TRAK1; HLA-B; TLR1; tcag7.1314; CD72; FLJ20674; MARCH3; HLA-F; PDLIM1; LRP10; KIAA0040; PIK3CG; STK32B; EVI5; LILRB1; CSDA; LARGE; NLRP1; SHOC2; 3.8-1; CYB5R1; C7orf23; PIK3CD; FADS3; LOC90925; RGL1; PDE4B; TRIO; FAM65A; LY86; TULP4; C17orf60; OFD1; HLA-DOA; ERO1LB; UNC119; VPREB1; CTGF; HIST2H2AA3; HLA-J; BTG2; FOXO1; GALNT14; PXDN; CIDEB; SCML2; SAV1; PRDX1; HLA-G; SCARF1; MBP; SPINT1; SLC35F2; GRB10; QRSL1; RASSF2; S100A13; CTBP2; DENND3; C10orf10; NEIL1; CYFIP1; CRIM1; MYO5C; ALDH3A2; GAB1; P4HA2; KIAA0495; LRRK1; MDM2; SLC35D2; VIPR1; ELK3; LILRB2; DUSP1; WFS1; KIAA0323; CPM; OGFRL1; ECHDC3; TST; BTN2A2; ZRANB1; LILRB3; TSC22D3; RAI14; ARSD; KMO; SSH3; BCL2L2; BCAS4; TGIF1; SCARB2; NPY; TCL6; CD58; MME; NPR1; LRIG1; KIF13A; SLC35E3; MYLK; IL1B; CELSR2; EHD3; FAM50B; IGHG1; CSF2RB; SCPEP1; CAST; 101 TRMT12; HLA-DRB3; SPIB; MYLIP; TERF2; BCAR3; NCF1; PIP5K1B; RAPGEF3; T-ALL MBD3 <0.001 0.01129 + up 2500 5 PSMB9; DRAM; KLHL2; GH1; MANBA; TAP2; STK38; GLRX; GNAI1; CD180; Suppl. Table 3 – page 4

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

SFMBT1; TPST1; IL6ST; GNA12; LDLRAP1; RHOB; DIP2C; IQCK; PPFIBP1; DRP2; C14orf106; DACT1; KANK2; P2RX1; IRF4; ARHGEF12; HHEX; S100A1; C14orf113; WASF1; HMHB1; C14orf132; ZNF274; STAG3; ZFP36; PHACTR1; TLR2; CELSR1; IRF7; LDOC1; DYRK3; HIST1H2BF; SYT11; COL5A1; HLA- DOB; LRMP; SCHIP1; CORO2B; GORASP1; CXorf21; NUAK2; DGCR6; SLC16A2; OR2A9P; HIST1H2BG; SYT1; PAOX; PARP1; PPP3CC; IRF6; C12orf49; ISG20; F13A1; ACOT9; MAP7D3; DGKD; KLF11; CYP2B7P1; OCA2; HLA-DQA1; IRS2; ALOX5; VRK2; PRKCE; PDK1; EWSR1; PCDH9; MALT1; RNF19B; SERPINI2; ZNF193; ABCB4; TLE1; FGD2; CYBB; PCSK6; ECM1; ACTR2; HLA-A; GSTM5; AKAP12; MGC5370; LMO2; NFKB1; PRO2268; UNC13B; PDE8B; CCR1; NCF2; COCH; PRDM2; BMPR2; STAT2; ELL3; RIN2; COBL; MTSS1; C9orf167; SGSH; C9orf45; SPPL2B; LTB4R; MAN1A1; EMP2; CD200; NCOA3; BMP2; RASL10A; CRMP1; ENTPD1; FGD1; P2RY14; ERG; ZSCAN16; HCK; CDC25C; SAMD4A; ST6GALNAC4; TGFBR2; TNS3; JAM2; HIST1H3D; CCDC81; RCAN1; NINJ1; KHDRBS3; SDC2; SSX4; NRGN; HLA-DRB4; GABBR1; PBX2; HLA-E; MPEG1; SLC43A1; AASS; CRAT; CLEC2D; SKIL; ODZ4; GPR132; EAF2; SERHL2; HIST1H2BE; FAM108B1; DDEF1; BASP1; CAP2; HIST1H2BN; MYRIP; IGSF3; DSP; OR1A1; MRC1; NOL4; IFIT3; KCTD7; BIN1; OLFML2A; LTBP2; FAM3C; MBNL2; TBXA2R; ZFP36L1; B2M; CSNK1G3; FOXP1; OR7A5; CEACAM21; HIST1H2BH; NIPSNAP3B; ENTPD3; SEMA5A; TMEM2; LTBR; MS4A1; CD86; CXCR6; TCF3; SEMA6D; RAG2; CD40; SLC7A7; TBC1D9; EPHB3; MMP11; IFIT2; ELOVL2; KCNS3; BACE1; ATP10B; PGCP; SLC11A1; HIST1H2AM; ID3; CSHL1; SLC15A2; NLRP2; GNAZ; HIST1H2AJ; GAS8; EFNB1; KLF2; ADAM19; HIST1H1C; HSPA2; HOMER2; EZR; IL8; SPRY4; IL13RA1; TP53I11; ASB13; VCL; PTPRG; IQSEC1; DDR1; SEMA3F; NEBL; C5orf4; ADCK2; HIST1H4H; FLJ20489; RHOQ; ITIH3; BLK; ULK2; FER1L3; ZNF467; SLC17A7; LDB2; CKMT2; B4GALT1; ANKRD55; REEP1; LOH3CR2A; IL3RA; KIAA0774; ECM2; KIAA0746; CYP2B6; ORAI3; CLOCK; C10orf56; KCNJ2; C11orf24; SRGAP2; FLJ10357; HIST1H2BI; TSSC1; FKSG49; MYO10; DPEP1; TXNIP; MUC5AC; CTSO; IRAK3; SH2D3C; USP10; EPHA7; GJC1; IGLJ3; MLLT4; ALDOC; MGP; MLPH; ITIH4; IFI30; C6orf145; RBM47; TGFB1I1; GIMAP4; BC37295_3; ZNF117; SIGLEC15; UTRN; EGFR; CLEC4E; AK5; FERMT1; ATP10D; SPTA1; NFATC4; OPHN1; STARD13; SLC2A1; FLT1; APBB2; SP4; IMPACT; TCL1B; PIK3IP1; KCNMB1; SEMA6A; KIF1B; AQP1; SUOX; IGKV1OR2-108; PTGS1; CD52; ERBB2; MS4A6A; HIST1H2BD; EVC; HEY2; SYNPO; LILRB4; DKK1; HAP1; RBMS3; C5; GLDC; LRRC17; SF3B3; NOLC1; FAM89B; TMEM70; NOL14; POLR2B; EXOSC10; CHERP; TNPO3; PRR4; C12orf41; TMEM134; ZNHIT1; USP47; POP4; C1orf77; C19orf10; PIH1D1; CHMP2A; SLC20A1; UPF1; ACACA; RRM1; YY1; TSN; YARS; UBE3A; PMS2L8; LUC7L2; UQCRFS1; CRKL; PANK2; RAB7A; BXDC5; GNG5; PSMC4; UCHL3; MAD2L1; AASDHPPT; PSMB7; CCT7;

Suppl. Table 3 – page 5

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

HSP90AA1; PI4KA; ITGB3BP; HNRNPA2B1; MED26; PSCD2; TARDBP; REST; RPL36; PPP1R7; NIF3L1; YLPM1; SFRS9; NCAPG2; FAM128B; NDUFA9; PIK3R4; DHPS; NFYB; POLR2I; RBBP4; COPG; TBC1D2B; ARS2; BMS1; ADRM1; H2AFV; HSPA9; CCT2; C19orf50; LOC130074; AMZ2; YY1AP1; ZXDC; TMEM194; CTCF; C19orf29; UQCRC1; FAM128A; RFC1; TXNL1; SCAMP1; CCDC90A; IMP3; ACLY; JOSD1; COX6A1; GTSE1; ALG8; DRG1; FBXO7; NDUFB7; SRP72; WDR6; COX4NB; CHCHD2; TCEA1; B3GAT3; BCL7B; PSMA5; CCDC72; UQCRQ; C19orf60; ATP6V1H; C14orf166; NF2; XPOT; KARS; HMGN2; DCTN2; NAB1; SNRPD1; POLR2F; MRPL20; MRPL11; TRMT5; PFN1; MTHFD1; HNRPA3P1; ATP5A1; OLA1; ZNF131; CYCS; SUMO2; MRPL4; GOLPH3; TCEB2; FASTKD1; PPP2CB; ICMT; PGD; PPME1; SUCLG1; MRPL23; ARPC1A; ZC3H4; BRD7; SNRPB; MORF4L2; MBTPS1; BAZ1B; DPM3; LOC645139; ANKMY2; MUM1; CCNB1; ELMO2; MRPS15; ASNSD1; AATF; PDCD5; LOC552889; ANP32E; C19orf56; RAD54L; ATP5H; C20orf149; MBD3; LIG1; TPI1; ACYP1; FLJ14154; TAF9; FHOD1; HSPE1; CFDP1; H2AFZ; ALDOA; NAT13; SHMT2; UQCRH; ARL1; HSPC152; EIF2AK1; STX10; HMGN4; RNF4; DAZAP1; COPS5; ATXN10; SSBP1; CASC3; RPN2; HNRNPR; SEC24C; UBP1; GMCL1; SUPT5H; YWHAQ; ZNF518A; UBE4A; RBM14; NAP1L4; KHSRP; SNRPG; LONP1; EIF4E2; MCM6; TBC1D25; GCSH; C1orf149; XRCC6; USP1; RPA1; MDH2; TUBA1B; TMEM106C; HNRPAB; TTC31; NSMAF; GMNN; USP39; DTYMK; PTOV1; PSMD14; YBX1; PMS2L1; NRD1; RNASEH2A; ATP5J2; ATP1A1; COX8A; COX17; GPBP1L1; LRRC40; ZNF146; PSMD1; PCMT1; NUP93; PPT1; PTCD3; HADH; DDX39; GMPS; C12orf29; SMC3; GLB1; METT11D1; TMEM160; BOLA1; RBBP8; ANAPC13; MED16; hCG_1776980; CDC34; TOMM70A; PATZ1; TRIM28; PPAT; FTO; TDG; TMEM208; RNMT; PGRMC1; PCID2; EXOSC4; TCP1; ARMC1; NDUFC2; TXNL4A; KATNB1; ARF4; RUFY1; DDX1; MTX1; SAFB2; TMEM5; NUBP2; THOC5; ATF4; POLRMT; SND1; RANBP5; DDX18; C1orf41; PRPF19; POLR3E; ZNF574; DGCR8; C11orf10; IHPK2; PSMD2; NDC80; TMPO; LARP1; LAGE3; UNC50; HAX1; UQCR; MAP2K2; NDUFS8; TADA3L; WDR18; THAP7; MGA; METAP1; PREB; SUMO1; WDR59; SNRPF; GSTP1; LOC730107; KHDRBS1; LSM3; CUL4A; BOLA2; NUP37; DGKZ; NXT1; STMN1; SHFM1; PSMD8; ATP5SL; FBXW2; FANCL; C9orf16; TERF2IP; CHCHD3; C16orf80; ILF2; MRPL3; LSM5; TUBA1C; PPP1CC; RSAD1; DPP3; TCEB1P; NIT2; MLF1IP; SAMM50; GARS; WDR82; PCNT; ACTL6A; MYOD1; MTERFD1; LSM1; SEC61A1; METTL5; RFXANK; SRPK1; DYNC1H1; ATP5G3; PIN1; C20orf24; TCEB1; ENTPD6; GAMT; CBX3; SAC3D1; NDUFS6; IKBKAP; UBA2; MRPL9; UNG; LASP1; PHF20; MEA1; TBCD; FARSA; MPHOSPH10; CALM2; TAOK3; TIMM13; MDH1; NOLA1; GORASP2; CCBL2; PANK4; CLEC3B; DBF4; GPR89B; UBL5; KEAP1; MSL2L1; RFXAP; GTPBP8; PAICS; NDUFA7; ARHGAP15; AOF2; EIF3M; GSS; TMOD1; OXSR1; FBL; CDC16; DGUOK; TTLL12; PSMC2; RTN4;

Suppl. Table 3 – page 6

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

POLR2H; METTL9; CUTA; COX6C; TAF2; RFC3; GCDH; GPR89A; TRIM33; EFTUD1; PSMB2; CHMP7; ADA; UBAP2; MRPL48; IDH2; PPIF; SSR2; SNRPD2; NDUFB6; HLTF; SAP130; STAU1; POM121L1; VDAC3; NCDN; LETM1; SPECC1L; FADD; MSH2; ARFGAP1; ANP32B; GNA15; MIF; ATP13A3; UBE2V2; KIAA0494; C16orf61; NDUFA13; RPIA; PRR14; CLNS1A; FDXR; DNAJB6; RTN3; KIAA0241; NDUFA3; C19orf53; ZC3H13; GADD45GIP1; SEC61G; TFG; C11orf48; SPAST; UFD1L; FBXO46; NCOR2; EXOSC8; HINT1; ASF1A; SLC3A2; ATF2; ZDHHC4; LEPROTL1; ADH5; SLC25A38; PCM1; HMG2L1; MRP63; ST13; HYOU1; ATIC; UBR4; GMDS; FAF1; RHOG; CNOT7; C1orf174; C11orf51; PMF1; DRAP1; COX11; KIAA0152; SIVA1; INTS9; RAP1GDS1; SLC7A1; LDHB; ANKRD27; PRMT7; GRSF1; LCMT1; DNAJC9; PAPSS1; RAD21; FADS2; NUP50; ATP6V1B2; TFPT; GNAQ; ETFB; LOC150759; SFI1; FDPS; LSM4; HN1; FDFT1; TM2D3; PAFAH1B3; CLPP; FBXL12; PTP4A2; SLC1A4; CD47; LANCL1; SEMA4D; MAPKAPK3; CDK5RAP3; C9orf78; PELO; PEX5 LOC552891; HPRT1; PRDX3; GOT1; NDUFA1; NDUFS5; ACAT1; APIP; HSDL2; PDHX; NDUFB2; COPS3; ADFP; COX7B; LAGE3; AIF1; SMS; RBBP7; UCHL5IP; PSMC5; UBE2A; ATP5J; HMGN1; ARMCX1; SOD1; ARPC5; BCAP31; RCOR1; HMGN3; PECI; HN1; SLC25A5; NDUFB8; EEF1E1; CCDC56; EBP; CD93; PSMG1; C4orf27; RWDD1; PGAM1; IRAK3; SLC9A6; PHB; FAM45B; AMPD3; NDUFA8; GALNT2; NFIL3; MYLIP; BFAR; CBLB; DLGAP4; HIP1; PTGDR; CD84; APOBEC3G; CDH11; ANGPT2; GRAMD1B; MICAL3; RAG2; MTMR3; LRRC8B; PCDH9; PCBP4; GLDC; AP1B1; RHBDL2; CLTC; CAPN3; LGR5; MPPED2; Normal BAZ2A 0.001 0 + up 1500 79 LHFPL2; CHST7; CHST2; STAP1; PTPRM; CENTG2 MME; CD52; MYH10; COL5A1; MPP1; DPEP1; AKAP12; PARD3; ITPR3; RAI14; MAGED1; SYNE2; HPS4; MYLK; FAM65A; DBN1; MDK; PXDN; IL1B; EGLN1; TCF4; HCP5; DDR1; KHDRBS3; ITIH4; EMP2; FGD1; BMPR2; FLOT1; EHD1; LRIG1; ARID5B; C14orf132; SLAMF7; DIP2C; SRRD; LDOC1; COBL; ZNF667; ODZ4; HLA-C; H2AFY2; RAPGEF3; PSMB9; KANK2; C10orf10; LRRN2; HLA-F; CORO2B; NRN1; HLA-A; IGFBP4; TJP2; PCBP4; GAS1; APOL6; ATRNL1; ITIH3; DOCK9; TIAM1; GOLGA3; GNA11; GCHFR; DEF8; HLA-J; HRK; PARD6A; TP53I11; LRP6; DRP2; RIN2; IGLL1; GTF2IRD1; SMTN; E2F1; RASIP1; KLF11; PLAC4; FADS3; IGKV1D-13; IGKV1OR15-118; 3.8-1; KIAA0562; STX12; STAM2; CDK7; AKAP11; TSPAN31; VPS24; MEMO1; EIF3D; MFSD1; TM9SF2; BZW2; VAMP3; IQGAP2; NSMAF; CARS2; ASAH1; VPS13D; ATRN; GUCY1A3; NFATC3; DNAJB6; RYBP; GSTK1; RASSF1; CEP70; UBA3; ARL8B; COPS7A; SRPRB; UPF3A; EMR2; MPG; IKBKB; ACAA1; JMJD1C; RASA1; MED13L; SMARCA2; RRAS2; TBC1D2B; SH3YL1; ARL6IP5; GALC; LY75; C1orf164; FEZ2; MLL BAZ2B <0.001 0 + up 750 131 PCDHGC3; PLXNC1 CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- T-ALL BAZ2B <0.001 0 + up 2000 561 DPB1; HLA-DMA; HLA-DRB5; CD79B; CD24; TCL1A; BTK; VPREB3; JUP;

Suppl. Table 3 – page 7

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

POU2AF1; TFEB; IGHM; CHD7; GALNAC4S-6ST; CTNNA1; TCF4; HLA-DQB1; EGLN1; PTPN18; STX3; HLA-DRB6; PFTK1; CD9; CD22; BACH2; HCP5; GNG7; AUTS2; RHBDF2; TRIM38; HLA-B; tcag7.1314; FLJ20674; HLA-F; PDLIM1; KIAA0040; PIK3CG; LARGE; 3.8-1; C7orf23; PIK3CD; FADS3; LOC90925; RGL1; PDE4B; FAM65A; LY86; TULP4; OFD1; KCTD15; ERO1LB; VPREB1; HLA-J; BTG2; FOXO1; GALNT14; PXDN; NUDT3; SCML2; SAV1; PRDX1; HLA-G; SCARF1; SPINT1; QRSL1; RASSF2; S100A13; GTF2IRD1; C10orf10; NEIL1; CYFIP1; CRIM1; MYO5C; ALDH3A2; P4HA2; MDM2; VIPR1; ELK3; WFS1; CPM; ECHDC3; TST; BTN2A2; ZRANB1; LILRB3; RAI14; KMO; GNA11; TCL6; CD58; MME; LRIG1; KIF13A; SLC35E3; MYLK; IL1B; CELSR2; IGHG1; CSF2RB; BCAR3; NCF1; PIP5K1B; RAPGEF3; PSMB9; KLHL2; AK1; TAP2; GNAI1; CD180; SFMBT1; TPST1; LDLRAP1; RHOB; DIP2C; IQCK; PPFIBP1; DRP2; RBM38; C14orf106; DACT1; KANK2; IRF4; ARHGEF12; S100A1; C14orf113; WASF1; C14orf132; ZNF274; PHACTR1; CELSR1; LDOC1; DYRK3; SYT11; COL5A1; LRMP; CORO2B; PRKCD; GORASP1; SLC16A2; OR2A9P; SYT1; PAOX; PARP1; IRF6; C12orf49; F13A1; DGKD; KLF11; CYP2B7P1; TCIRG1; ALOX5; PDK1; EWSR1; MALT1; ABCB4; TLE1; FGD2; CYBB; ADRBK1; C3orf37; SMAD3; PCSK6; ECM1; HLA-A; GSTM5; AKAP12; NAV1; MGC5370; NFKB1; SH2B2; PDE8B; NCF2; SRRD; COCH; BMPR2; ELL3; RIN2; COBL; C9orf167; SGSH; SPPL2B; EMP2; CBR1; RASL10A; CRMP1; ENTPD1; FGD1; ZNF672; ZSCAN16; HCK; CDC25C; SAMD4A; ST6GALNAC4; TGFBR2; JAM2; CCDC81; RCAN1; NINJ1; TBC1D1; KHDRBS3; SSX4; NRGN; HLA-DRB4; GABBR1; AASS; CRAT; ODZ4; SMTN; EAF2; SERHL2; DDEF1; BASP1; HIST1H2BN; MXD3; IGSF3; DSP; OR1A1; NOL4; IFIT3; BIN1; HPS4; LTBP2; FAM3C; ZFP36L1; OR7A5; CEACAM21; ENTPD3; SEMA5A; MS4A1; CD86; CXCR6; TCF3; SEMA6D; RAG2; CD40; MICALL1; APBB1IP; EPHB3; IFIT2; ELOVL2; KCNS3; BACE1; ATP10B; SLC11A1; HIST1H2AM; ID3; NLRP2; GNAZ; GAS8; EFNB1; KLF2; ADAM19; HIST1H1C; HSPA2; EZR; TAP1; IL8; SPRY4; TREX1; TP53I11; IQSEC1; DDR1; SEMA3F; NEBL; C5orf4; ADCK2; FLJ20489; ITIH3; BLK; M-RIP; NARFL; ZNF467; SLC17A7; B4GALT1; ANKRD55; REEP1; LOH3CR2A; KIAA0774; ECM2; KIAA0746; CYP2B6; CLOCK; C10orf56; KCNJ2; SRGAP2; CENTA1; TSSC1; FKSG49; DPEP1; MUC5AC; SH2D3C; USP10; GJC1; MLLT4; MGP; MLPH; ITIH4; IFI30; BC37295_3; DNTT; SIGLEC15; EGFR; FERMT1; NFATC4; OPHN1; APBB2; SP4; TCL1B; KCNMB1; PSMB8; IGKV1OR2-108; CD52; ERBB2; MS4A6A; EVC; SYNPO; ALG6; MED23; OBFC1; NSUN5C; HSPBAP1; COX7A2L; MBTPS1; ZC3H11A; SC5DL; ANKMY2; MUM1; SECISBP2; ELMO2; ASNSD1; LOC552889; C19orf56; TAF9; FHOD1; ARL1; COPS5; CRBN; RPN2; FLJ11286; UBP1; ZNF518A; SS18; KIAA1797; UBE4A; RBM7; C1orf149; DZIP3; PRKACB; TALDO1; LRBA; TTC31; NSMAF; SERTAD2; CEPT1; PMS2L1; C2orf25; HSD17B7; NSUN5B; GPBP1L1; LRRC40; CASD1;

Suppl. Table 3 – page 8

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

IDH1; ZNF146; AMY1A; PPT1; NMI; PTCD3; HADH; C12orf29; GLB1; METT11D1; ANAPC13; MED16; TOMM70A; PATZ1; LOC220594; FTO; C20orf19; SACM1L; TDG; RNMT; PCID2; EDEM3; GTF2F2; ARF4; STK38L; TES; LOC728411; SAFB2; TMEM5; IQWD1; POLRMT; SND1; ZNF83; SLC25A44; DDX18; POLR3E; ZNF574; IHPK2; UNC50; BCKDHB; UQCR; SLC33A1; TADA3L; KIAA0999; TMED5; MGA; OSBPL2; PTPRC; WDR59; FAM48A; CUL4A; LIPC; ATP5SL; FBXW2; BIRC2; CASP4; RSAD1; TCEB1P; CTR9; C1orf103; HIBCH; THSD1; MYOD1; CEP63; FAM62A; SAMSN1; GARNL4; RFXANK; CD46; INPP4A; IKBKAP; SLC25A46; P2RX4; DMXL2; LASP1; PHF20; TAPBPL; MPHOSPH10; TAOK3; ERCC5; OSBP; SCP2; EPM2AIP1; GORASP2; CCBL2; CSGlcA-T; INSIG2; GPR89B; VPS8; SLC11A2; MSL2L1; ICAM2; TANK; REXO2; ARHGAP15; PTTG1IP; EIF3M; TMOD1; OXSR1; MDM1; CDC16; IFRD1; DGUOK; RTN4; FNDC3A; PIP4K2A; FNBP1; PFKP; C19orf2; TAF2; GCDH; GPR89A; TRIM33; DOCK2; CHMP7; SSR2; STAU1; VDAC3; PIK3CB; NCDN; FADD; SLC2A3P1; GNA15; KIAA0494; CEP70; PRR14; ITGAE; CLNS1A; DNAJB6; TSC22D1; KIAA0241; ZC3H13; TFG; ZBTB20; SPAST; EXOSC8; ATF2; POLI; IL2RG; DPYD; ZDHHC4; TLE3; CTSW; C12orf11; LEPROTL1; PCM1; ST13; CASP8; UBR4; RHOG; SELL; TMEM135; C1orf174; TRAF3IP3; DFFB; TBXAS1; ANKRD27; SIGIRR; GOLGA8G; GRSF1; TFRC; STAM; ITPR2; SSFA2; ABCC1; PAPSS1; ATP6V1B2; OSBPL3; STAT3; GNAQ; LOC150759; SLC25A20; ATP2C1; FDFT1; TM2D3; DHRS7; ARHGEF3; FBXL12; CD47; LANCL1; IMPA1; SEMA4D; MAPKAPK3; CDK5RAP3; NOTCH1; AGL; STAT5A; CMAH; C14orf135; LZTFL1; NUCB2; TOX DBN1; HMG4L; NCAPH; TOP2A; MKI67; KIF4A; TPX2; COL1A1; CDCA3; MAGED1; FANCE; ERCC6L; HJURP; MYBL2; KIF11; CENPE; MYH10; AURKB; Relapse BAZ2B <0.001 0 + up 750 24 AKR1B1; EXO1; MFSD1; IDH1; CEP70; LEPROT S100A4; IGFBP7; MAP3K5; SECTM1; NLRP3; PTGES3; SFXN3; CHMP1B; CCR DNMT3A <0.001 0 + up 400 16 SMEK1; POLE; ZNF273; MCM10; ZNF43; PRPF4B; ZNF675; DBN1 MME; CD52; MYO5C; FHIT; COL5A1; DNTT; VAMP5; ALOX5; ELK3; SCHIP1; PXDN; STK32B; EGLN1; DUSP26; TCF4; HCP5; GIMAP4; KHDRBS3; SH3TC1; SLC35E3; FGD1; BMPR2; NAV1; tcag7.1314; ZNF467; PTP4A3; DIP2C; MGC5370; BTN2A2; PXN; RGL1; LDOC1; TREML2; LTB; RAPGEF3; KANK2; C10orf10; PDE4B; IGFBP4; SEMA6A; XYLT1; PTER; CEP70; KIAA0125; UBA3; BRPF1; MLL DNMT3B <0.001 0.06117 + up 400 51 PIGB; TBC1D2B; TPP2; HK2; PLXNC1 MME; CD52; MYO5C; EXDL2; SERPINB9; FHIT; COL5A1; DNTT; MPP1; DPEP1; AKAP12; RAI14; SMAD1; ZNF274; ZNF135; GFOD1; ALOX5; ITGA5; ELK3; POLE; GRAMD1B; SCHIP1; MYLK; FAM65A; MDK; PXDN; IL1B; STK32B; EGLN1; DUSP26; TCF4; ID3; HCP5; GIMAP4; DAB2; DDR1; KHDRBS3; SH3TC1; ITIH4; SLC35E3; MYO1B; EMP2; FGD1; ABCG2; BMPR2; NAV1; tcag7.1314; MLL HDAC1 0.006 0 + up 2000 407 ZNF467; PTP4A3; ZNF257; ASB13; LRIG1; LIG4; ARID5B; C14orf132; SUOX;

Suppl. Table 3 – page 9

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

CASK; SLAMF7; SETBP1; STAT4; DIP2C; MGC5370; EFNA1; BTN2A2; PXN; RGL1; SRRD; PRO2268; LDOC1; PLCH1; COBL; ZNF667; ODZ4; IGHA1; HLA-C; TREML2; H2AFY2; APP; KIAA0427; DYRK3; ERG; RAPGEF3; KANK2; C10orf10; ABCG1; LRRN2; HLA-F; CCND2; ATN1; POU4F1; PDE4B; SPANXA1; FAM127A; TBL1X; UTRN; CORO2B; NRN1; HLA-A; IGFBP4; PECAM1; ZNF117; ITGA6; DAPK1; FAM129A; SEMA6A; SPTA1; IGHG3; PCBP4; SERPINB6; GAS1; RASL10A; A2M; APOL6; ATRNL1; ITIH3; GRIK5; TNFRSF21; CRIM1; CYTL1; ASB9; GNA11; IFIT2; NOS2A; HERC5; GPHN; MED9; SCARF1; OPTN; EPHA7; TMEM140; LARGE; ARHGEF17; PTGDR; ST3GAL6; KIAA1166; HLA-J; WFS1; OAS3; SH3BP5; LGALS3BP; HRK; ECM1; FLJ20489; MRC1; FAM127B; GBP1; MCTP2; P2RY14; IFIH1; PDXK; TMEM156; OSBPL10; SOD2; TP53I11; LRP6; CEBPE; F2RL1; DRP2; NEO1; RIN2; ARHGAP24; DLGAP2; EFNB1; PIP3-E; NOD1; GTF2IRD1; SMTN; CD200; CTNS; DLG3; TSPAN5; RASIP1; NUDT11; KLF11; TBC1D9; PLAC4; FRMD4B; FADS3; IGKV1D-13; LOC57228; MDM2; IGKV1OR15-118; 3.8-1; NPDC1; SEMA3F; SLC22A5; ZSCAN16; GABBR1; NR3C2; MUC5AC; NEIL1; NINJ1; KIAA0774; MLXIP; BMPR1B; C16orf67; TIAF1; C14orf45; PRKCZ; GAB1; KIAA1466; PTPRM; VPREB3; KCNK3; ZNF253; HLA- G; PDK3; ELOVL2; NEDD9; NCF2; SAV1; SIGLEC15; FERMT1; TCL1A; ARHGEF4; MYT1L; TXNRD3; NTN2L; IFI6; PTPRK; MARCKS; CEACAM6; DDEF1; RAG1; SLC25A46; PPCS; VPS13B; GOLGB1; EIF2B4; FLJ11506; DAP3; C1orf149; ATP5F1; BRD9; B3GAT3; NFU1; EIF4H; SEC11A; TSC22D2; ANXA6; TAF9; ALDOA; PIGT; U2AF2; BUD31; BTBD1; ETFA; KIAA0999; AURKAIP1; ZNF313; C19orf50; BRP44L; TGOLN2; CHCHD3; NDUFA10; SRP19; PRPF38B; MTMR6; TCERG1; PDCD6IP; EIF3K; ATR; STAMBP; FXR1; CHORDC1; CDV3; GRINL1A; GNL2; NOL12; C2orf24; BID; SPG11; JARID2; ALG8; LYPLA1; RNASEH1; LEPROTL1; CHMP1A; SCP2; PLEKHB2; NDUFS3; FAM32A; PRPF40A; UBE4A; PHB2; CAPZA1; C9orf16; C22orf28; UFC1; DDX47; RTCD1; IDH3A; SAP18; LRRC47; HN1L; CIB1; NDUFB5; ATP5G2; MRPS30; R3HDM2; CHD4; UQCRC2; MAPRE1; MRPS34; ATP5B; DUSP12; TRAF3IP3; TMED5; CYB5R3; DNAJA3; RER1; ZDHHC4; EIF3I; RBM22; ESD; XPOT; RPIA; COPZ1; MDH2; ZRF1; TXNDC14; NEUROD1; DPP3; MRPL3; EIF6; CLNS1A; NSUN5; RAB14; TCF25; ANAPC5; HSBP1; CMAS; SHMT2; PMS1; PRR13; UCHL3; PPID; EIF3M; MRPS12; FDX1; DNAJA2; TSPAN3; COX5A; WBSCR22; TUFM; BXDC5; SPCS1; ARPC2; CEP63; EFHA1; HADH; MASP1; IMMT; ANKMY2; PPP1CA; AKR7A2; EIF2B1; RMND5A; SLC25A3; GABARAPL2; STRAP; UNC119B; CDK7; DIAPH1; PTDSS1; SYF2; IQGAP1; HMOX2; MEMO1; C15orf15; C20orf43; TWF1; ETF1; EIF3D; EXOC3; POP5; TM9SF2; PWP1; DCTN3; ATP5SL; NSMAF; LPCAT1; PELI1; SCYE1; ITGAE; PCGF1; CS; DNAJB6; ATP6V1F; UBA3; ARL8B; SRPRB; APEH; UPF3A; LOC440354; CLASP2; IKBKB; CYC1; ACAA1; PIGB; PABPC4; PTPRC; MAP4; TPP2; ADAM10; ARL6IP5; MBNL1

Suppl. Table 3 – page 10

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; CD24; TCL1A; BTK; VPREB3; JUP; POU2AF1; CHD7; TCF4; HLA-DQB1; LAMC1; SLC27A3; EGLN1; PTPN18; HLA- DMB; HLA-DRB6; CD9; PTPRE; HCP5; ENG; HLA-B; TLR1; tcag7.1314; HLA-F; PDLIM1; STK32B; LARGE; TSPAN14; 3.8-1; FADS3; RGL1; ADCY6; PDE4B; C17orf60; HLA-DOA; ERO1LB; HIST2H2AA3; HLA-J; BTG2; PXDN; FAM49A; CIDEB; SCML2; C1orf38; HLA-G; SCARF1; S100A13; C10orf10; CRIM1; MYO5C; ALDH3A2; GAB1; MDM2; SLC35D2; VIPR1; ELK3; WFS1; OGFRL1; ECHDC3; BTN2A2; ZRANB1; LILRB3; RAI14; ARSD; SSH3; GNA11; NPY; MME; NPR1; LRIG1; KIF13A; SLC35E3; MYLK; IL1B; HLA-DRB3; MYLIP; TERF2; RAB13; RAG1; RAPGEF3; DRAM; TAP2; TPST1; PPFIBP1; DRP2; KANK2; S100A1; C14orf113; C14orf132; TLR2; EPHB4; CELSR1; IRF7; LDOC1; DYRK3; HIST1H2BF; COL5A1; SCHIP1; OR2A9P; HIST1H2BG; IRF6; CYP2B7P1; OCA2; HLA-DQA1; ALOX5; LIMD1; EGFL7; ZNF193; ABCB4; FGD2; CYBB; ADRBK1; PCSK6; CRTAP; ECM1; GSTM5; NAV1; PRO2268; PDE8B; CCR1; NCF2; BMPR2; STAT2; RIN2; COBL; C9orf167; IFI35; LTB4R; EMP2; BMP2; RASL10A; ENTPD1; FGD1; P2RY14; ERG; CDC25C; HIST1H3D; SSX4; NRGN; GABBR1; PBX2; CRAT; ODZ4; GPR132; SERHL2; DDEF1; HIST1H2BN; IGSF3; DSP; OR1A1; MRC1; NOL4; IFIT3; OLFML2A; OR7A5; ENTPD3; SEMA5A; CD86; CXCR6; SEMA6D; CD40; TBC1D9; EPHB3; IFIT2; DLG1; CBX3; NDUFS6; IKBKAP; SLC25A46; UBA2; MRPL9; C13orf23; PHF20; SUB1; BZW1; CALM2; MRPL16; HDAC1; ERCC5; OSBP; SCP2; EPM2AIP1; MDH1; DBF4; GPR89B; UBL5; VPS8; MSL2L1; DECR1; NDUFA6; NDUFA7; ARHGAP15; AOF2; COX7C; EIF3M; MDM1; CDC16; DGUOK; PSMC2; RTN4; POLR2H; TROVE2; COX6C; TAF2; GPR89A; TRIM33; EFTUD1; PSMB2; DOCK2; MRPL48; SSR2; SNRPD2; STAU1; MRPL13; SLC2A3P1; MIF; UBE2V2; KIAA0494; C16orf61; NDUFA13; RPIA; ITGAE; CLNS1A; DNAJB6; NDUFA3; C19orf53; SEC61G; TFG; C11orf48; SPAST; UFD1L; EXOSC8; MTMR6; ATF2; ZDHHC4; LEPROTL1; SLC25A38; PCM1; MRP63; ATIC; UBR4; FAF1; BRP44L; DRAP1; KIAA0152; INTS9; SEC61B; LDHB; ABCD3; DCUN1D1; GRSF1; LCMT1; RAD21; NUP50; ATP6V1B2; TFPT; SFI1; FDPS; THYN1; LSM4; FBXL12; PTP4A2; CD47; LANCL1; IMPA1; INSIG1; T-ALL HDAC1 <0.001 0.04189 + up 1000 281 SEMA4D; CDK5RAP3; C9orf78; NUCB2 MGC29506; CD2AP; EXDL2; SV2A; SERPINB9; MYH10; PRKCH; PARD3; ITPR3; TNFRSF14; ST3GAL5; ZNF135; HYI; TRAF5; SYNE2; NEDD4; C11orf75; ARMCX2; ZNF329; GIMAP4; DAB2; MYO1B; YES1; RHOF; BLVRA; RYK; NDFIP1; ZNF257; ASB13; LIG4; CASK; SLAMF7; STAT4; FAM117A; PTPLA; ZNF512B; ZNF415; SALL2; TSPAN7; PLCH1; GPR56; ZNF667; IGHA1; HLA-C; TREML2; SPAG16; SLC5A3; XPA; ABLIM1; FBXO21; RAB15; ZNF529; LTB; GIMAP6; CCDC92; RAPGEF3; EPAS1; ABCG1; DHCR7; NOTCH2; NET1; MLL HDAC5 0.004 0 + up 2500 592 RAB11A; FGFR1; PLCG1; CD27; TJP2; PECAM1; C6orf32; ITGA6; DAPK1;

Suppl. Table 3 – page 11

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

GIMAP5; FAM129A; SEMA6A; LST1; PHF17; IGHG3; ELOVL5; DSG2; ETV5; GAS1; A2M; APOL6; CTDSPL; RICS; ZBTB20; DOCK9; C2orf3; GRIK5; CD247; IFITM2; UBE2E3; ASB9; IFITM1; BEX4; IFIT2; GPHN; STAT5B; PLXND1; GCHFR; RAB27A; GTDC1; PRKCA; MRPS6; ARHGEF17; DEF8; FZD6; PTGDR; ST3GAL6; KIAA1166; LRP4; NF1; ENOSF1; OAS3; SH3BP5; HRK; NUDT6; PRDX4; ICAM3; GBP1; MCTP2; PVRIG; MFHAS1; ARHGAP29; ST8SIA4; B4GALT6; TMEM156; DLG5; OSBPL10; EHD2; F2RL1; C2CD2; MAST4; DRP2; ARHGAP24; DLGAP2; NOD1; HDGFRP3; GLS; CD8A; BCL11B; FAM102A; EDG1; TSPAN5; PIK3R3; NUDT11; CASP10; FUT8; CNN3; ACP6; PLAC4; IGKV1D-13; IGKV1OR15-118; NPDC1; LAX1; RBM9; MYBL1; SLC22A5; PTPRF; IL23A; ENPP4; SFXN1; FYB; MUC5AC; TTC9; TMEFF1; FAT; BMPR1B; KIAA1128; CSTB; FADS1; C16orf67; PTK7; C14orf45; ARNTL2; SEPP1; PSRC1; SEPT6; KIAA1466; PTPRM; CLIP4; KCNK3; ZNF253; C7orf44; RUNX3; PDK3; AJAP1; DGKA; LCK; SGPP1; KLHL3; FERMT1; PAWR; TXNRD3; NTN2L; FLJ14213; IFI6; TCF7; PTPRK; CENPE; CEACAM6; ASS1; EPOR; SCAND1; C17orf48; BECN1; GGNBP2; STXBP3; DCXR; MAPK9; BCR; VPS16; GTF2F1; ARSD; MOAP1; EHBP1L1; LAMP1; DNM1L; UBE2D2; CDIPT; DNAJC4; GNB2; NTAN1; MAFF; CCDC28A; MAP1LC3B; FPGS; NCOR1; PDXDC1; RNF19B; SCAMP2; NPTN; ATP6V0C; ARHGAP25; PWP2; RBM23; LRMP; ZDHHC7; SH3BGRL; TAX1BP3; SFRS17A; SCAMP3; TTLL3; BCL11A; VARS; SNX26; ADAM17; LAT2; ASL; HEATR1; SPSB3; KIN; SLC35F2; PCBP1; TLN1; AKT1; HEBP1; EIF1B; ARHGEF18; SWAP70; HMGA1; C16orf58; CPSF3L; PPCS; TBC1D16; AKAP1; EIF2B4; SKIL; CAPN1; JMJD2C; EXOC1; TLR2; PNPLA6; ABCF2; NEU1; MED15; MYO9B; TBC1D1; MSH5; ATP6V0B; IMPDH1; INSR; PPP3CB; EIF3CL; LRRFIP1; PLEKHM1; PPP3CA; NCOA3; PIGT; ULK1; HMG20B; U2AF2; C14orf94; ARHGEF6; AURKAIP1; RP2; KCTD15; ZNF783; FNTA; NDUFA10; MAPKAP1; GDI2; TXNDC13; DRG2; GLG1; RASGRP2; PCYOX1L; PDCD2; TSR1; PRPF38B; ERCC2; TCERG1; GPS1; ELOVL1; KRI1; FAM118A; SCAMP4; ARD1A; LOC728844; SPAG9; GNL2; ADD1; NR3C1; SPG11; GCN5L2; C5orf15; USP25; COMT; DDX28; RNF7; TRIP4; ZFP36; SLC12A9; CHMP1A; MAN2A2; ZMYND8; RPS6KA4; CTAGE5; CAPNS1; HCK; STX7; TAF11; UBE2E1; PRPF40A; PRKCD; FLJ20323; C22orf28; SEC61A2; UFC1; NUBP1; EML3; ERP29; INPP5B; LRRC47; HECTD3; HMHB1; MTM1; PPP2R3C; ATP5G2; FRAT1; MSH6; CHD4; MKNK2; GPX1; SLC25A11; PAK1IP1; TARBP1; GGA2; EIF3B; PRKCSH; CDC123; CD81; CLTA; MICAL1; ASPSCR1; EIF4A1; ABI1; PLCG2; MMP17; LY86; CCDC22; SOLH; SETDB1; KDELR1; GGA1; KPNA3; CTSB; RAB4B; KIAA0100; IRAK1; MGC3032; NIPBL; TOMM20; RBM22; GTPBP4; PEX11B; CTSA; CYB5R1; MYCBP2; ATP5S; MEF2D; ARPC1B; ADI1; COPZ1; ZRF1; TNIP2; EIF6; C1orf108; RAB5B; TCF25; PPP2R5C; TRIM8; DYNLT1; CTGF; OS9; PRR13; PDHX; MAN2C1; SDF4; NCBP2; GIT2; GTPBP6;

Suppl. Table 3 – page 12

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PTPLB; BLK; RNF40; QTRTD1; CECR5; CBX4; NAGPA; CCNB1IP1; POLR3C; WDR19; ARPC3; BANK1; EZR; LMO2; HLX; MANBA; BASP1; VPS37B; NCK2; SEH1L; IFNGR1; ARHGAP1; SYNGR2; EAF2; PPP1CA; EIF2B1; PPFIA1; RMND5A; CDKN1A; DBI; UNC119; SMPD2; GABARAPL2; GLA; HEXB; UTP6; DERA; CDK7; DIAPH1; SLC25A6; CAP1; FAM53B; STAT6; SNX17; SYF2; ELAC2; WDR45L; PES1; MMP11; ARHGAP17; RABEP2; CASP9; MEMO1; SUPT4H1; CLIP1; ATG12; C20orf43; PTPN6; TMEM149; EFHC1; TRIM34; MEF2A; OTUB1; SPIB; NIP7; SMURF1; MFSD1; VAMP8; HBEGF; PSCD4; CHKB; HDAC9; TSPO; ARL2; ADPGK; NSF; CARS2; TPD52L2; NUP214; CSRP2; ARFGAP2; FES; DUSP22; VPS13D; DDX21; PYCARD; EI24; MFSD10; LRCH4; FLJ42627; ATP8A1; FRAT2; CS; QARS; RHBDF2; AHCY; BCL7A; M6PRBP1; EHD4; CYBA; DGKD; GLT25D1; RASSF1; MPV17; TBCC; AMPD2; ABR; TBC1D9B; BRPF1; RNFT1; DUSP3; DDEF2; DVL1; MARCH3; GDF11; MYH9; GMIP; SH3BGRL3; RPS6KA1; FLT3; CLASP2; IKBKB; MYO1F; PLXNB2; ACAA1; CYB561D2; JMJD1C; HCLS1; RASA1; PUS1; CLEC2D; VNN1; SMARCA2; ZNF394; ABAT; IGF2BP3; COQ2; MAP4; ASXL1; LOC100137047- PLA2G4B; RPP40; GLT8D1; BCAS4; SIRT7; IDUA; SH3YL1; C22orf9; PRKCE; KCTD5; KCNK12; MAN2B1; ZEB2; MAST3; C12orf5; AK2; CDKN1B; PTCH1; CD72; C1orf164; ADCY9; FEZ2; TUBB6; FAIM; GPM6B; SCPEP1; NLRP3; PCDHGC3; DAD1; PCDHGA1; MPZL1; ABHD4 SOCS2; ACSL5; CCND2; RNASET2; GALNT1; C1orf38; LTB4R; HPCAL1; SH2B3; XBP1; HHEX; EPHB4; EGFL7; SMC6; ITPR1; GPX1; SYNGR1; C13orf18; INTS3; FUCA1; CD97; UTRN; PTPN2; NUCKS1; HDAC4; MMD; CYFIP2; MAGEF1; PBK; ELOVL5; TOR3A; ITPKB; CSRP1; ARL4C; UCHL5; SS18L2; MAP1A; PTBP2; SCCPDH; SYNJ2; FH; TUSC4; RHOBTB1; TRIB2; ODC1; TMEM183A; D4S234E; E2A-PBX1 HDAC4 <0.001 0 + up 400 51 ACAD8; PITPNC1; ADARB1; FAT MME; CD52; MYO5C; FHIT; COL5A1; DNTT; SMAD1; GFOD1; ALOX5; ITGA5; ELK3; SCHIP1; FAM65A; STK32B; EGLN1; DUSP26; TCF4; HCP5; GIMAP4; SLC35E3; MYO1B; FGD1; NAV1; tcag7.1314; ZNF467; ASB13; HIF1A; SUOX; MGC5370; EFNA1; RGL1; PRO2268; APP; ERG; RAPGEF3; HLA-F; CCND2; POU4F1; PDE4B; UTRN; HLA-A; ITGA6; SEMA6A; SPTA1; SERPINB6; RASL10A; CRIM1; CYTL1; GNA11; IFIT2; NOS2A; SCARF1; GRAMD4; ITGAE; MLL HDAC4 <0.001 0 + up 500 60 DNAJB6; CDKN2D; UCK2; CAPG; SLC4A7; ADAM10 PAX5; CD19; BLNK; BTK; IGHM; CD72; FLJ20674; MARCH3; EVI5; CYB5R1; LOC90925; LY86; TULP4; ADCY9; KCTD15; ERO1LB; VPREB1; GALNT14; SLC35F2; ZEB2; ALDH3A2; VIPR1; ECHDC3; TST; KMO; BCAS4; CD58; IL1B; EHD3; CSF2RB; SCPEP1; SPIB; NCF1; KLHL2; HMG2L1; CD2AP; CASP8; UBR4; CNOT6; CD300A; RHOG; SELL; ZNF512B; ENOSF1; TSPAN7; RARRES3; SEPT6; SIGIRR; STAM; LCMT1; CENTB1; RAD21; NF1; FGFR1; GNAQ; STAT5B; T-ALL HDAC7 <0.001 0.0326 + up 500 91 LOC150759; SFI1; GNPDA1; ICAM3; TCF20; PLCG1; EVL; CCDC92; LAX1;

Suppl. Table 3 – page 13

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

RHOH; TRGV9; SLC9A3R1; NDFIP1; TRGC2; TARP; IL27RA; SEMA4D; FAM117A; LCP2; RGS10; CDK5RAP3; SELPLG; NOTCH1; LIME1; STAT5A; CD6; SEPW1; TOX; TCF7; DENND2D; IL23A; BIN2; LCK; SCD; CD3D CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; BTK; CD79A; VPREB3; JUP; PLCG2; CIITA; POU2AF1; TFEB; IGHM; CHD7; GALNAC4S-6ST; CTNNA1; RIPK2; TCF4; HLA-DQB1; INSR; HLX; LAMC1; STX7; SLC27A3; EGLN1; LAPTM5; PTPN18; LAT2; HLA-DMB; BANK1; TSPAN13; STX3; HLA- DRB6; PLXNB2; PFTK1; CD9; PTPRE; HCP5; GNG7; AUTS2; PTK2; RHBDF2; LILRA6; LILRA2; TRIM38; ENG; HLA-B; TLR1; tcag7.1314; CD72; FLJ20674; MARCH3; DYNLT1; HLA-F; FHL1; PDLIM1; LRP10; KIAA0040; STK32B; PHLPP; LILRB1; CSDA; SOCS2; LARGE; NLRP1; TSPAN14; 3.8-1; FADS3; RGL1; ADCY6; PDE4B; FAM65A; LY86; ADCY9; C17orf60; OFD1; KCTD15; HLA-DOA; ERO1LB; UNC119; VPREB1; CTGF; HIST2H2AA3; HLA-J; BTG2; GALNT14; PXDN; FAM49A; CIDEB; SCML2; C1orf38; SAV1; HLA-G; SCARF1; MBP; SPINT1; GRB10; RASSF2; S100A13; KIAA1033; CTBP2; PSD3; DENND3; CDKN1A; CDYL; C10orf10; NEIL1; RFTN1; CYFIP1; CRIM1; MYO5C; ALDH3A2; GAB1; P4HA2; KIAA0495; LRRK1; MDM2; SLC35D2; VIPR1; ELK3; LILRB2; WFS1; IRF8; CPM; OGFRL1; ECHDC3; BTN2A2; ZRANB1; LILRB3; TSC22D3; RAI14; ARSD; KMO; SSH3; BCL2L2; FES; GNA11; NPY; TCL6; MME; NPR1; LRIG1; KIF13A; SLC35E3; MYLK; IL1B; FAM50B; IGHG1; CAST; TRMT12; GSN; HLA-DRB3; SPIB; MYLIP; TERF2; BCAR3; RAB13; NCF1; PIP5K1B; RAPGEF3; DRAM; KLHL2; GH1; TAP2; GNAI1; CD180; SFMBT1; SLC2A5; TPST1; IL6ST; GNA12; LDLRAP1; DIP2C; PPFIBP1; DRP2; DACT1; KANK2; ARHGEF12; HHEX; S100A1; C14orf113; WASF1; HMHB1; C14orf132; ZNF274; STAG3; FUCA1; PHACTR1; TLR2; CELSR1; IRF7; LDOC1; DYRK3; HIST1H2BF; SYT11; COL5A1; RNASET2; HLA-DOB; LRMP; SCHIP1; CORO2B; CXorf21; NUAK2; DGCR6; SLC16A2; OR2A9P; HIST1H2BG; PAOX; PPP3CC; IRF6; C12orf49; ISG20; F13A1; ACOT9; KLF11; CYP2B7P1; TCIRG1; UNC93B1; OCA2; HLA- DQA1; BRF1; ALOX5; LIMD1; RNF19B; SERPINI2; EGFL7; ZNF193; ABCB4; TLE1; FGD2; CYBB; SMAD3; PCSK6; ECM1; HLA-A; GSTM5; NAV1; HIST1H2BK; MGC5370; LMO2; SH2B2; PRO2268; UNC13B; PDE8B; CCR1; NCF2; SRRD; PPM1F; BMPR2; STAT2; ELL3; RIN2; COBL; MTSS1; DUSP6; C9orf167; SGSH; SPPL2B; IFI35; LTB4R; MAN1A1; EMP2; CBR1; HIST2H2BE; BMP2; RASL10A; CRMP1; ENTPD1; GPM6B; FGD1; P2RY14; ERG; HCK; CDC25C; CTSB; SAMD4A; JAM2; HIST1H3D; CCDC81; RCAN1; KHDRBS3; TNS1; RALB; SSX4; NRGN; HLA-DRB4; GABBR1; LHFP; PBX2; HLA-E; MPEG1; AASS; DUSP3; CRAT; KCNA5; ODZ4; GPR132; EAF2; SERHL2; HIST1H2BE; DDEF1; CAP2; HIST1H2BN; MXD3; MYRIP; IGSF3; DSP; OR1A1; MRC1; NOL4; T-ALL SMARCC1 0.003 0.08862 + up 2500 962 CYB5R2; IFIT3; KCTD7; BIN1; OLFML2A; LTBP2; FAM3C; FLT3; TBXA2R;

Suppl. Table 3 – page 14

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

FOXP1; OR7A5; CEACAM21; HIST1H2BH; NIPSNAP3B; ENTPD3; SEMA5A; TMEM2; LTBR; MS4A1; CD86; CXCR6; SEMA6D; CD40; MICALL1; SLC7A7; TBC1D9; EPHB3; IFIT2; ELOVL2; KCNS3; BACE1; ATP10B; SLC11A1; HIST1H2AM; ID3; CSHL1; SLC15A2; NLRP2; GNAZ; HIST1H2AJ; GAS8; EFNB1; KLF2; ADAM19; HIST1H1C; HSPA2; HOMER2; SPRY4; IL13RA1; ASB13; VCL; PTPRG; DDR1; SEMA3F; NEBL; C5orf4; ADCK2; HIST1H4H; FLJ20489; RHOQ; BLK; ULK2; FER1L3; SPTLC2; ZNF467; TRPM2; SLC17A7; LDB2; FLOT2; CKMT2; B4GALT1; ANKRD55; REEP1; ITGA5; LOH3CR2A; IL3RA; KIAA0774; ECM2; KIAA0746; CYP2B6; CLOCK; C10orf56; KCNJ2; C11orf24; CENTA1; HIST1H2BI; FKSG49; MYO10; DPEP1; MUC5AC; IRAK3; SH2D3C; INTS3; EPHA7; GJC1; MGP; MLPH; ITIH4; IFI30; C6orf145; RBM47; UGCG; TGFB1I1; GIMAP4; BC37295_3; DNTT; ZNF117; SIGLEC15; UTRN; TBC1D16; EGFR; CLEC4E; LOC643641; AK5; PLVAP; FERMT1; ATP10D; SPTA1; NFATC4; OPHN1; STARD13; SLC2A1; FLT1; SP4; IMPACT; TCL1B; PIK3IP1; TNFSF13; ALDH3B1; KCNMB1; SEMA6A; KIF1B; AQP1; SUOX; IGKV1OR2-108; PTGS1; CD52; CENTD1; ERBB2; MS4A6A; HIST1H2BD; EVC; HSPG2; SYNPO; DKK1; HAP1; CDS2; RBMS3; C5; LRRC17; SCN1B; MRPS34; PCNP; THOC7; SLC38A2; SMARCC1; SUPT6H; EIF4E; SF3B3; NOLC1; FAM89B; HDAC2; POLR2B; FUBP3; MAPBPIP; EXOSC10; CHERP; TNPO3; C12orf41; GLOD4; SNRPE; ZNHIT1; PARL; POP4; C1orf77; C19orf10; PIH1D1; CHMP2A; UPF1; ACACA; YY1; TSN; YARS; FAM60A; UBE3A; PMS2L8; LUC7L2; UQCRFS1; CRKL; GPI; RPL24; BXDC5; GNG5; PSMC4; UCHL3; AASDHPPT; RUNX1; QRICH1; TXNDC1; PSMB7; TPRKB; CCT7; PI4KA; ITGB3BP; HNRNPA2B1; PSCD2; TARDBP; REST; PPP1R7; NIF3L1; PAAF1; YLPM1; SFRS9; FAM128B; RNASEH2B; HYPK; MORF4; NDUFA9; DHPS; NFYB; TTC33; BTBD1; POLR2I; RBBP4; COPG; VPS13B; TBC1D2B; ARS2; BMS1; ADRM1; H2AFV; HSPA9; CCT2; C19orf50; LOC130074; ADSS; YY1AP1; MRPL22; ZXDC; CTCF; C15orf44; C19orf29; UQCRC1; TIMM17A; NPEPPS; TXNL1; SCAMP1; CCDC90A; IMP3; ACLY; BCKDHA; ZBTB11; COX6A1; ALG8; DRG1; FBXO7; PAIP1; NDUFB7; SRP72; WDR6; ISG20L2; DCTN6; SRP9; COX4NB; CHCHD2; C9orf82; BCL7B; PSMA5; CCDC72; UQCRQ; C14orf166; ERBB2IP; NF2; XPOT; KARS; EIF4G2; DCTN2; SEPT7; SNRPD1; POLR2F; MRPL20; MARCKSL1; MRPL11; TRMT5; PFN1; HNRPA3P1; ATP5A1; OLA1; TMED3; ATP5E; ZNF131; RIF1; CYCS; SUMO2; MRPL4; IVNS1ABP; GOLPH3; TCEB2; PGD; C3orf28; ALG6; SUCLG1; MRPL23; ARPC1A; ZC3H4; BRD7; SNRPB; COX7A2L; MBTPS1; BAZ1B; LOC645139; FLJ11506; SKP1; SECISBP2; PSMA4; MRPS15; ASNSD1; AATF; PDCD5; LOC552889; ANP32E; MBD3; LIG1; TPI1; FLJ14154; TAF9; HSPE1; CFDP1; ALDOA; R3HDM1; NAT13; SHMT2; UQCRH; HSPC152; EIF2AK1; STX10; HMGN4; RNF4; DAZAP1; COPS5; ATXN10; SSBP1; CASC3; HNRNPR; SEC24C; UBP1; GMCL1; SUPT5H; YWHAQ; UBE4A; RBM14; NAP1L4; COX6B1; KHSRP;

Suppl. Table 3 – page 15

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

SNRPG; LONP1; CDV3; FKSG30; HSPA8; GCSH; C1orf149; XRCC6; USP1; POLR1D; RPA1; MDH2; TUBA1B; HNRPAB; NSMAF; USP39; PTOV1; LDHA; PSMD14; YBX1; PMS2L1; C2orf25; RNASEH2A; ATP5J2; ATP1A1; LRRC40; NUP93; YWHAH; PPT1; NDUFB4; PTCD3; HADH; DDX39; NDUFA4; SMC3; METT11D1; NGRN; TMEM160; ALDH18A1; BID; hCG_1776980; CDC34; TOMM70A; TBL2; PATZ1; TRIM28; FTO; SACM1L; TDG; TMEM208; RNMT; PCID2; EDEM3; TCP1; GTF2F2; ARMC1; GSPT1; NDUFC2; KATNB1; ARF4; DDX1; MAGOHB; MTX1; SAFB2; NUBP2; THOC5; ATF4; POLRMT; SND1; RANBP5; SLC25A44; DDX18; ZMYM2; C1orf41; PRPF19; POLR3E; ZNF574; C11orf10; IHPK2; PSMD2; SNX4; EID1; TMPO; LARP1; HAX1; BCKDHB; MAP2K2; NDUFS8; WDR18; MGA; PREB; SUMO1; WDR59; SNRPF; LOC730107; KHDRBS1; LSM3; GOT2; CUL4A; MTHFD2; NUP37; NXT1; STMN1; SHFM1; PSMD8; PRKRA; ATP5SL; FBXW2; C9orf16; TERF2IP; CCDC86; CHCHD3; C16orf80; ILF2; MRPL3; LSM5; GATAD2A; TUBA1C; PPP1CC; RSAD1; DPP3; TCEB1P; NIT2; CTR9; SAMM50; GARS; WDR82; ARFGEF1; NIPSNAP1; ACTL6A; MYOD1; SERP1; METTL5; RFXANK; DYNC1H1; ATP5G3; PIN1; INPP4A; C20orf24; TCEB1; PRUNE; DLG1; CBX3; SAC3D1; IKBKAP; SLC25A46; UBA2; TTC27; MRPL9; UNG; DMXL2; C13orf23; CEP57; C12orf47; FARSA; BZW1; MPHOSPH10; CALM2; MRPL16; HDAC1; SCP2; TSPYL4; TIMM13; EPM2AIP1; AMD1; MDH1; NOLA1; GORASP2; CCBL2; PANK4; CLEC3B; DBF4; GPR89B; UBL5; KEAP1; POGK; MSL2L1; RFXAP; AZIN1; PAICS; NOL11; NDUFA6; NDUFA7; AOF2; COX7C; EIF3M; TMOD1; OXSR1; FBL; MDM1; DGUOK; PSMC2; POLR2H; METTL9; CUTA; COX6C; TAF2; RFC3; GCDH; GPR89A; TRIM33; EFTUD1; PSMB2; DOCK2; UBAP2; MRPL48; IDH2; PPIF; SSR2; SNRPD2; NDUFB6; HLTF; STAU1; VDAC3; SPECC1L; MRPL13; TRIM37; MSH2; SLC2A3P1; C5orf13; ANP32B; MIF; ATP13A3; THEM2; UBE2V2; KIAA0494; C16orf61; NDUFA13; RPIA; CLNS1A; DNAJB6; RTN3; KIAA0241; ZBED4; NDUFA3; C19orf53; ZC3H13; GADD45GIP1; SEC61G; TFG; SPAST; NCOR2; EXOSC8; ATF2; ATMIN; ZDHHC4; C12orf11; LEPROTL1; SLC25A38; PCM1; HMG2L1; MRP63; ST13; HYOU1; ATIC; PGM1; UBR4; GMDS; CNOT6; CNOT7; C1orf174; PMF1; MTMR2; DRAP1; KIAA0152; INTS9; SEC61B; LDHB; GRSF1; LCMT1; DNAJC9; RAD21; NUP50; ATP6V1B2; TFPT; LOC150759; FDPS; LSM4; PAFAH1B3; CLPP; FBXL12; PTP4A2; CD47; LANCL1; SEMA4D; HIRA; C9orf78 CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; BTK; CD79A; SNX2; VPREB3; JUP; PLCG2; CIITA; NCF4; POU2AF1; TFEB; IGHM; CHD7; GALNAC4S-6ST; CTNNA1; RIPK2; TCF4; HLA-DQB1; INSR; HLX; LAMC1; GGA2; STX7; SLC27A3; EGLN1; LAPTM5; PTPN18; LAT2; HLA-DMB; BANK1; T-ALL SMARCC2 0.009 0 + up 2500 980 TSPAN13; STX3; HLA-DRB6; PLXNB2; PFTK1; CD9; PTPRE; BACH2; HCP5;

Suppl. Table 3 – page 16

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

GNG7; PTK2; RHBDF2; LILRA6; LILRA2; TRIM38; TLR1; tcag7.1314; CD72; FLJ20674; MARCH3; DYNLT1; SIPA1; CSRP2; HLA-F; CDK9; FHL1; PDLIM1; KIAA0040; STK32B; LILRB1; LARGE; NLRP1; 3.8-1; FADS3; RGL1; ADCY6; PDE4B; GPD1L; LY86; ADCY9; C17orf60; OFD1; KCTD15; HLA-DOA; ERO1LB; VPREB1; CTGF; HIST2H2AA3; DOK3; HLA-J; BTG2; FOXO1; FAM49A; CIDEB; SCML2; C1orf38; PRDX1; SCARF1; MBP; SPINT1; GRB10; QRSL1; S100A13; ZMYND8; KIAA1033; PSD3; DENND3; HEXB; CDKN1A; CDYL; C10orf10; NEIL1; CYFIP1; CRIM1; ALDH3A2; GAB1; GPX1; P4HA2; KIAA0495; CYBA; LRRK1; MDM2; SYNGR1; SLC35D2; VIPR1; ELK3; WFS1; IRF8; KIAA0323; OGFRL1; ECHDC3; TST; BTN2A2; ZRANB1; LILRB3; RAI14; ARSD; ETS2; KMO; SSH3; BCAS4; TGIF1; FES; GNA11; NPY; TCL6; NPR1; KIF13A; SLC35E3; IL1B; FAM50B; IGHG1; SCPEP1; CAST; GSN; HLA-DRB3; SPIB; MYLIP; TERF2; BCAR3; RAB13; NCF1; ATP6V0D1; PIP5K1B; RAPGEF3; DRAM; KLHL2; PFKL; MANBA; AK1; TAP2; CD180; TPST1; LDLRAP1; IQCK; PPFIBP1; DRP2; C14orf106; DACT1; KANK2; ARHGEF12; HHEX; S100A1; C14orf113; CLCN7; WASF1; HMHB1; C14orf132; PHACTR1; TLR2; EPHB4; CELSR1; IRF7; LDOC1; DYRK3; HIST1H2BF; COL5A1; HLA-DOB; LRMP; SCHIP1; CXorf21; NUAK2; DGCR6; SLC16A2; OR2A9P; HIST1H2BG; SYT1; PAOX; IRF6; C12orf49; F13A1; ACOT9; DGKD; KLF11; CYP2B7P1; UNC93B1; OCA2; HLA-DQA1; BRF1; ALOX5; HBEGF; PRKCE; PDK1; LIMD1; PCDH9; SERPINI2; ZNF193; MFSD10; ABCB4; TLE1; FGD2; EHD4; CYBB; ADRBK1; SMAD3; PCSK6; CRTAP; ECM1; ACTR2; GSTM5; NAV1; HIST1H2BK; MGC5370; IGF2BP3; LMO2; SIDT2; SH2B2; PRO2268; UNC13B; PDE8B; CCR1; NCF2; SRRD; SFRS2IP; MAP3K5; PPM1F; BMPR2; STAT2; ELL3; RIN2; COBL; MTSS1; TAZ; KIAA1539; C9orf167; SGSH; C9orf45; SPPL2B; IFI35; LTB4R; EMP2; NCOA3; CBR1; HIST2H2BE; RASL10A; CRMP1; ENTPD1; GPM6B; FGD1; MAST3; P2RY14; HCK; CDC25C; SAMD4A; ST6GALNAC4; TNS3; JAM2; HIST1H3D; CCDC81; NINJ1; KHDRBS3; SDC2; TNS1; SSX4; NRGN; HLA-DRB4; GABBR1; LHFP; MPEG1; SLC43A1; DUSP3; CRAT; CLEC2D; SKIL; PEX16; ODZ4; SMTN; TRABD; GPR132; EAF2; SERHL2; HIST1H2BE; FAM108B1; BASP1; CAP2; HIST1H2BN; MXD3; SMURF1; MYRIP; IGSF3; DSP; OR1A1; MRC1; NOL4; CYB5R2; IFIT3; KCTD7; BIN1; OLFML2A; LTBP2; FAM3C; FLT3; MBNL2; FOXP1; OR7A5; HIST1H2BH; NIPSNAP3B; ENTPD3; SEMA5A; LTBR; CD86; CXCR6; TCF3; SEMA6D; CD40; SLC7A7; APBB1IP; TBC1D9; EPHB3; MMP11; DUSP22; IFIT2; ELOVL2; BACE1; ATP10B; PGCP; SLC11A1; RNFT1; GLT25D1; HIST1H2AM; ID3; CSHL1; SLC15A2; NLRP2; GNAZ; HIST1H2AJ; GAS8; EFNB1; ADAM19; HIST1H1C; HSPA2; HOMER2; EZR; IL8; SPRY4; IL13RA1; VCL; SEMA3F; NEBL; C5orf4; ADCK2; HIST1H4H; RHOQ; ITIH3; BLK; ULK2; FER1L3; SPTLC2; ZNF467; TRPM2; SLC17A7; CKMT2; ANKRD55; REEP1; LOH3CR2A; IL3RA; KIAA0774; ECM2; KIAA0746; CYP2B6; C10orf56; KCNJ2; C11orf24; SRGAP2; FLJ10357;

Suppl. Table 3 – page 17

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

CENTA1; HIST1H2BI; FKSG49; DPEP1; MUC5AC; APAF1; IRAK3; SH2D3C; USP10; EPHA7; GJC1; IGLJ3; MLLT4; MGP; MLPH; ITIH4; IFI30; C6orf145; RBM47; UGCG; TGFB1I1; BC37295_3; ZNF117; SIGLEC15; UTRN; TBC1D16; EGFR; CLEC4E; AK5; PLVAP; FERMT1; SPTA1; NFATC4; OPHN1; STARD13; SLC2A1; APBB2; SP4; TCL1B; TNFSF13; ALDH3B1; KCNMB1; SEMA6A; KIF1B; SAMHD1; AQP1; SUOX; IGKV1OR2-108; C1orf78; PTGS1; PCDHGC3; PCDHGA1; ERBB2; MS4A6A; EVC; HSPG2; SYNPO; LILRB4; DKK1; HAP1; TGIF2; RBMS3; C5; LRRC17; SCN1B; PCNP; THOC7; SLC38A2; SMARCC1; NDUFAF1; SUPT6H; RABGEF1; DYNC1I2; SF3B3; RCHY1; FAM89B; NCOR1; POLR2B; FUBP3; EXOSC10; CHERP; PRR4; C12orf41; TMEM134; USP47; PARL; POP4; C1orf77; SYNE2; PSIP1; SLC20A1; ACACA; YY1; TSN; YARS; FAM60A; UBE3A; LUC7L2; UQCRFS1; CRKL; PANK2; RPL24; RAB7A; BXDC5; KIAA0528; GNG5; R3HDM2; CYFIP2; PROSC; QRICH1; PSMB7; CCT7; HSP90AA1; PI4KA; HNRNPA2B1; PSCD2; SETD5; TARDBP; REST; RPL36; PPP1R7; C5orf3; YLPM1; SFRS9; COX7A2; FAM128B; MORF4; MAN1A2; NDUFA9; PIK3R4; DHPS; BTBD1; POLR2I; RBBP4; NCOA1; ARS2; BMS1; H2AFV; HSPA9; CCT2; LOC130074; ZFAND6; APPBP2; NOSIP; ADSS; YY1AP1; MRPL22; CTCF; C15orf44; UQCRC1; MUT; NPEPPS; TXNL1; SCAMP1; UGP2; ACLY; JOSD1; H3F3A; ZBTB11; COX6A1; ALG8; DRG1; FBXO7; PAIP1; CCDC93; SRP72; WDR6; ISG20L2; DCTN6; SRP9; CHCHD2; C9orf82; TCEA1; B3GAT3; BCL7B; PSMA5; CCDC72; UQCRQ; C19orf60; C14orf166; ERBB2IP; NF2; XPOT; NCK1; KARS; SUCLA2; EIF4G2; DCTN2; NAB1; SEPT7; STIM1; HMGN3; MRPL20; MRPL11; C11orf73; PFN1; HNRPA3P1; ATP5A1; OLA1; ATP5E; ZNF131; RIF1; CYCS; SUMO2; GOLPH3; TCEB2; ICMT; ALG6; MED23; SUCLG1; ZC3H4; BRD7; HSPBAP1; COX7A2L; MBTPS1; BAZ1B; DPM3; LOC645139; ZC3H11A; C1orf9; SKP1; SECISBP2; ELMO2; PSMA4; MRPS15; ASNSD1; AATF; LOC552889; ANP32E; C19orf56; MBD3; TPI1; TAF9; HSPE1; CFDP1; ALDOA; R3HDM1; NAT13; UQCRH; HSPC152; EIF2AK1; CSTF3; HMGN4; MFAP3; RNF4; DAZAP1; COPS5; ATXN10; SSBP1; CASC3; RPN2; FLJ11286; HNRNPR; HDAC7; UBP1; SUPT5H; YWHAQ; BCAS2; UBE4A; RBM14; NAP1L4; COX6B1; KHSRP; VPS45; SNRPG; LONP1; CDV3; FKSG30; HSPA8; RBM7; C1orf149; XRCC6; USP1; POLR1D; RPA1; DZIP3; TUBA1B; HNRPAB; TTC31; NSMAF; SERTAD2; PTOV1; LDHA; PSMD14; YBX1; NRD1; C2orf25; ATP5J2; ATP1A1; NSUN5B; GPBP1L1; LRRC40; CASD1; C16orf57; PSMD1; PCMT1; NUP93; YWHAH; PPT1; NDUFB4; NMI; PTCD3; HADH; NDUFA4; SMC3; NGRN; NFATC2IP; TDRD3; ANAPC13; hCG_1776980; TOMM70A; PATZ1; TRIM28; FTO; RAB5A; SACM1L; TDG; PCID2; EDEM3; TCP1; GTF2F2; ARMC1; GSPT1; ZC3HAV1; NDUFC2; ARF4; CCDC53; RUFY1; DDX1; SAFB2; THOC5; PUS3; ATF4; POLRMT; ZNF83; RANBP5; SLC25A44; DDX18; UBR5; ZMYM2; C1orf41; POLR3E; ZNF574; DGCR8; C11orf10; IHPK2;

Suppl. Table 3 – page 18

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PSMD2; SNX4; EID1; TMPO; STK17A; LARP1; UNC50; HAX1; MAP2K2; SLC33A1; NDUFS8; TADA3L; TMED5; MGA; SUMO1; WDR59; LOC730107; KHDRBS1; FAM48A; LSM3; GOT2; CUL4A; NUP37; DGKZ; UBA5; NXT1; ATXN7; PSMD8; PRKRA; FBXW2; TERF2IP; CHCHD3; C16orf80; ILF2; MRPL3; LSM5; GATAD2A; TUBA1C; PPP1CC; RSAD1; TCEB1P; CTR9; HIBCH; SAMM50; WDR82; ACTL6A; MYOD1; FAM62A; SERP1; METTL5; DYNC1H1; CD46; ATP5G3; INPP4A; C20orf24; TCEB1; PRUNE; DLG1; CBX3; SAC3D1; IKBKAP; SLC25A46; UBA2; TTC27; SETMAR; MRPL9; DMXL2; C13orf23; LASP1; CEP57; PHF20; MEA1; BZW1; MPHOSPH10; CALM2; MRPL16; HDAC1; ERCC5; SCP2; TSPYL4; EPM2AIP1; AMD1; MDH1; NOLA1; GORASP2; CCBL2; CLEC3B; GPR89B; UBL5; VPS8; MAPK6; CSGALNACT2; MSL2L1; NOL11; TANK; NDUFA6; REXO2; FTHP1; ARHGAP15; AOF2; COX7C; EIF3M; TMOD1; OXSR1; FBL; MDM1; CDC16; JARID2; DGUOK; PSMC2; RTN4; POLR2H; METTL9; CUTA; C19orf2; TROVE2; TAF2; GCDH; GPR89A; TRIM33; EFTUD1; PSMB2; DOCK2; CHMP7; ADA; UBAP2; GIMAP6; MRPL48; TUBA1A; IDH2; SSR2; SNRPD2; NDUFB6; STAU1; MRPL13; SMARCAL1; TRIM37; MSH2; SLC2A3P1; ANP32B; MIF; ATP13A3; THEM2; UBE2V2; KIAA0494; SLC5A3; C16orf61; NDUFA13; PRR14; CLNS1A; CDC25B; AZI2; DNAJB6; RTN3; KIAA0241; NDUFA3; C19orf53; ZC3H13; TFG; C11orf48; SPAST; UFD1L; FBXO46; CDR2; NCOR2; HINT1; ATF2; ATMIN; ZDHHC4; C12orf11; LEPROTL1; SLC25A38; PCM1; HMG2L1; GTF3A; ST13; HYOU1; ATIC; UBR4; FAF1; RHOG; TMEM135; CNOT7; C1orf174; DRAP1; KIAA0152; INTS9; LDHB; RARRES3; FADS1; SEPT6; ABCD3; GRSF1; LCMT1; CENTB1; ABCC1; RAD21; FADS2; NUP50; NF1; TFPT; LOC150759; FDPS; THYN1; KCTD9; LSM4; KIFAP3; SSBP3; FDFT1; TM2D3; SC4MOL; EVL; FAM130A1; RCN1; PTP4A2; CD47; LANCL1; EXTL2; INSIG1; SEMA4D; LCP2; C9orf78; CMAH; NUCB2; HMGCS1 EXDL2; LMAN1; FKTN; ACD; MASP1; ARPC1B; C16orf33; POLR3K; IMPDH1; 2nd_AML SMARCD2 <0.001 0 + up 1500 10 BLOC1S1 CD74; HLA-DRA; HLA-DRB1; CD19; BLNK; HLA-DPA1; C14orf139; MEF2C; BTK; SNX2; JUP; TFEB; CTNNA1; RIPK2; HLA-DQB1; LAMC1; INPP5D; GGA2; CUL1; BCL11A; LAPTM5; PTPN18; NUBP1; ROGDI; GNG7; LILRA6; TRIM38; ENG; HLA-B; TLR1; PPP3CA; DYNLT1; SIPA1; CSRP2; CDK9; FHL1; KIAA0040; REEP5; C17orf60; KCTD15; HLA-DOA; DOK3; CIDEB; NUDT3; PRDX1; HLA-G; GRB10; CDKN1A; FPGS; MEF2A; GPX1; CYBA; IRF8; FES; CECR5; ATP6V0D1; RCBTB1; PSMB9; LDLRAP1; MEF2D; RBM38; C14orf106; C14orf113; PRKCD; CXorf21; ZBED1; RPS6KA1; TBC1D5; HIP1; RAB4B; NAV1; GALNT12; CLIP4; ASRGL1; FAM13A1; GPA33; HEG1; ITGAE; AZI2; WWOX; PLS1; RYK; CR2; TXK; ATHL1; CDR2; PALLD; KIF21B; FZD6; CD300A; RCBTB2; PAQR3; DENND1C; ZNF529; LRRC1; GOLGA8G; DEXI; ITPR2; WBP5; PDLIM5; PKIA; T-ALL SMARCA1 <0.001 0 + up 750 159 RASGRP1; OSBPL3; LOC440295; GNPDA1; S100A11; SSBP3; CHRNA5; ATP8A2;

Suppl. Table 3 – page 19

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PLCG1; CLGN; CD1E; PCBP3; PIP4K2C; TRGV9; TRGC2; EXTL2; ZNF167; TARP; LIMA1; SNX10; SLC19A2; SELPLG; AGL; NOTCH3; C9orf78; VAT1; CMAH; ATP1B1; C14orf135; LZTFL1; CD247; EPHB6; CD2; CD6; GATA3; GALNT6; NGFRAP1; ITK; DENND2D; CHI3L2; CD28; AQP3; USP20; PTPN7; BIN2; LAT; BCL11B; PRKCQ; LCK; SCD; CD7; TRAT1; UBASH3A; CD3E; TRD@; MAL; SH2D1A; CD3D DBN1; ZNF253; CDCA3; MAGED1; CDC25B; ERCC6L; HJURP; MYH10; SALL2; Relapse SMARCA2 <0.001 0.01129 + down 750 13 EXO1; IGFBP7; MFSD1; LEPROT CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; BTK; CD79A; SNX2; VPREB3; JUP; PLCG2; CIITA; NCF4; POU2AF1; IGHM; CHD7; GALNAC4S-6ST; RIPK2; TCF4; HLA-DQB1; INSR; HLX; LAMC1; GGA2; STX7; SLC27A3; BCL11A; EGLN1; LAPTM5; PTPN18; LAT2; HLA-DMB; BANK1; TSPAN13; STX3; HLA-DRB6; PFTK1; CD9; CD22; PTPRE; BACH2; HCP5; GNG7; PTK2; RHBDF2; LILRA6; LILRA2; TRIM38; ENG; HLA-B; TLR1; tcag7.1314; FLJ20674; MARCH3; SIPA1; CSRP2; HLA-F; CDK9; FHL1; PDLIM1; KIAA0040; PIK3CG; STK32B; LILRB1; SOCS2; LARGE; NLRP1; TSPAN14; 3.8-1; FADS3; RGL1; ADCY6; PDE4B; FAM65A; LY86; ADCY9; C17orf60; KCTD15; HLA-DOA; ERO1LB; VPREB1; CTGF; HIST2H2AA3; DOK3; HLA-J; BTG2; FOXO1; PXDN; CLCC1; FAM49A; CIDEB; NUDT3; SCML2; C1orf38; HLA-G; SCARF1; MBP; SPINT1; GRB10; S100A13; KIAA1033; PSD3; DENND3; CDKN1A; CDYL; C10orf10; NEIL1; CRIM1; MYO5C; ALDH3A2; GAB1; GPX1; P4HA2; CYBA; LRRK1; MDM2; SYNGR1; SLC35D2; VIPR1; ELK3; LILRB2; WFS1; IRF8; OGFRL1; ECHDC3; BTN2A2; LILRB3; RAI14; ARSD; ETS2; KMO; SSH3; TGIF1; FES; GNA11; SCARB2; NPY; TCL6; MME; NPR1; KIF13A; SLC35E3; MYLK; IL1B; FAM50B; CSF2RB; TRMT12; GSN; HLA-DRB3; SPIB; MYLIP; TERF2; BCAR3; RAB13; NRIP1; RAG1; NCF1; PIP5K1B; RAPGEF3; DRAM; KLHL2; MANBA; TAP2; GNAI1; CD180; SCARB1; SLC2A5; TPST1; APP; LDLRAP1; DIP2C; PPFIBP1; DRP2; ARHGAP25; C14orf106; DACT1; KANK2; ARHGEF12; HHEX; S100A1; C14orf113; CLCN7; SPI1; WASF1; C14orf132; ZNF274; STAG3; FUCA1; TLR2; EPHB4; CELSR1; IRF7; LDOC1; DYRK3; HIST1H2BF; SYT11; COL5A1; HLA-DOB; SCHIP1; CXorf21; NUAK2; DGCR6; SLC16A2; OR2A9P; HIST1H2BG; PAOX; IRF6; C12orf49; F13A1; ACOT9; KLF11; CYP2B7P1; UNC93B1; OCA2; HLA-DQA1; ALOX5; PDK1; EWSR1; LIMD1; PCDH9; RNF19B; SERPINI2; EGFL7; ZNF193; ABCB4; TLE1; FGD2; EHD4; CYBB; ADRBK1; SMAD3; PCSK6; CRTAP; HIP1; ECM1; ACTR2; HLA-A; GSTM5; NAV1; HIST1H2BK; MGC5370; LMO2; SH2B2; PRO2268; UNC13B; PDE8B; CCR1; NCF2; SRRD; SFRS2IP; PPM1F; BMPR2; STAT2; ELL3; RIN2; COBL; MTSS1; 101 KIAA1539; DUSP6; C9orf167; SGSH; C9orf45; SPPL2B; IFI35; LTB4R; MAN1A1; T-ALL SMARCD1 0.001 0 + up 2500 8 EMP2; CD200; NCOA3; CBR1; HIST2H2BE; BMP2; RASL10A; CRMP1; ENTPD1;

Suppl. Table 3 – page 20

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

FGD1; P2RY14; ERG; ZSCAN16; HCK; CDC25C; CTSS; SAMD4A; ST6GALNAC4; TNS3; JAM2; HIST1H3D; KHDRBS3; IRF1; SDC2; TNS1; SSX4; NRGN; HLA-DRB4; GABBR1; PBX2; HLA-E; SLC43A1; DUSP3; CRAT; KCNA5; ODZ4; SMTN; TRABD; GPR132; SERHL2; HIST1H2BE; FAM108B1; DDEF1; CAP2; JAK2; HIST1H2BN; MYRIP; IGSF3; DSP; OR1A1; MRC1; NOL4; CYB5R2; IFIT3; KCTD7; OLFML2A; LTBP2; FLT3; MBNL2; TBXA2R; B2M; HPCAL1; FOXP1; OR7A5; CEACAM21; HIST1H2BH; NIPSNAP3B; ENTPD3; SEMA5A; LTBR; MS4A1; CD86; CXCR6; TCF3; SEMA6D; CD40; SLC7A7; POLD4; APBB1IP; TBC1D9; EPHB3; IFIT2; BACE1; ATP10B; PGCP; SLC11A1; HIST1H2AM; ID3; CSHL1; NLRP2; GNAZ; HIST1H2AJ; GAS8; EFNB1; ADAM19; HIST1H1C; HSPA2; HOMER2; STAP1; EZR; IL8; SPRY4; IL13RA1; TP53I11; ASB13; PTPRG; DDR1; SEMA3F; NEBL; C5orf4; ADCK2; HIST1H4H; FLJ20489; RHOQ; ITIH3; BLK; ULK2; FER1L3; SPTLC2; ZNF467; TRPM2; SLC17A7; LDB2; FLOT2; CKMT2; ANKRD55; REEP1; ITGA5; LOH3CR2A; IL3RA; KIAA0774; ECM2; KIAA0746; CYP2B6; CLOCK; C10orf56; KCNJ2; C11orf24; FLJ10357; CENTA1; HIST1H2BI; GNG11; FKSG49; MYO10; DPEP1; TXNIP; MUC5AC; IRAK3; SH2D3C; INTS3; USP10; EPHA7; GJC1; IGLJ3; MLLT4; ALDOC; MGP; MLPH; ITIH4; IFI30; RBM47; UGCG; GIMAP4; BC37295_3; DNTT; ZNF117; SIGLEC15; UTRN; TBC1D16; EGFR; CLEC4E; AK5; PLVAP; FERMT1; ATP10D; SPTA1; NFATC4; OPHN1; STARD13; SLC2A1; FLT1; APBB2; SP4; TCL1B; TNFSF13; ALDH3B1; SEMA6A; SAMHD1; AQP1; SUOX; IGKV1OR2-108; C1orf78; PTGS1; CD52; CENTD1; ERBB2; MS4A6A; HIST1H2BD; EVC; HSPG2; HEY2; SYNPO; LILRB4; DKK1; HAP1; TGIF2; PSCD4; RBMS3; LRRC17; SCN1B; NDUFV2; PPM1G; PCGF1; MRPS34; PCNP; THOC7; SLC38A2; SMARCC1; NDUFAF1; SUPT6H; DYNC1I2; SF3B3; NOLC1; FAM89B; NCOR1; PIGH; POLR2B; FUBP3; MAPBPIP; C1D; EXOSC10; CHERP; UCRC; PRR4; C12orf41; SNRPE; ZNHIT1; USP47; PARL; POP4; C1orf77; PIH1D1; CHMP2A; SLC20A1; SLC30A9; ACACA; YY1; TSN; YARS; FAM60A; UBE3A; LUC7L2; UQCRFS1; CRKL; PANK2; STAMBP; GPI; RPL24; RAB7A; BXDC5; KIAA0528; GNG5; R3HDM2; ACAT2; PSMC4; CYFIP2; QRICH1; PSMB7; TPRKB; CCT7; HSP90AA1; PI4KA; HNRNPA2B1; SLC4A7; PSCD2; SETD5; TARDBP; REST; PPP1R7; PAAF1; YLPM1; SFRS9; COX7A2; FAM128B; HYPK; TBCE; MORF4; MAN1A2; TMCO1; NDUFA9; PIK3R4; UBB; DHPS; NFYB; BTBD1; POLR2I; RBBP4; COPG; VPS13B; ARS2; SGSM2; BMS1; ADRM1; H2AFV; HSPA9; CCT2; C19orf50; LOC130074; NOSIP; ADSS; PSMA7; YY1AP1; MRPL22; ZXDC; CTCF; C15orf44; C19orf29; UQCRC1; TIMM17A; NPEPPS; TXNL1; SCAMP1; ACLY; JOSD1; BCKDHA; H3F3A; ZBTB11; COX6A1; ALG8; DRG1; FBXO7; PAIP1; NDUFB7; SRP72; WDR6; ISG20L2; DCTN6; SRP9; COX4NB; CHCHD2; C9orf82; B3GAT3; BCL7B; PSMA5; CCDC72; UQCRQ; C19orf60; C14orf166; ERBB2IP; NF2; XPOT; KARS; EIF4G2; DCTN2; SEPT7; NDUFB8; SNRPD1; POLR2F;

Suppl. Table 3 – page 21

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

MRPL20; MARCKSL1; PFN1; HNRPA3P1; ATP5A1; OLA1; ATP5E; ZNF131; CYCS; SUMO2; GOLPH3; TCEB2; FASTKD1; ICMT; PGD; ALG6; PPME1; SUCLG1; ZC3H4; BRD7; SNRPB; MORF4L2; NSUN5C; HSPBAP1; COX7A2L; MBTPS1; BAZ1B; DPM3; LOC645139; FLJ11506; C1orf9; SKP1; SECISBP2; ELMO2; PSMA4; MRPS15; ASNSD1; AATF; LOC552889; ANP32E; ATP5H; MBD3; TPI1; FLJ14154; TAF9; HSPE1; CFDP1; ALDOA; R3HDM1; NAT13; SHMT2; UQCRH; HSPC152; EIF2AK1; STX10; HMGN4; BTG3; RNF4; DAZAP1; COPS5; ATXN10; SSBP1; CASC3; C18orf10; RPN2; HNRNPR; UBP1; YWHAQ; BCAS2; UBE4A; RBM14; NAP1L4; COX6B1; KHSRP; VPS45; SNRPG; LONP1; CDV3; EIF4E2; C1orf149; XRCC6; USP1; POLR1D; RPA1; MDH2; TUBA1B; HNRPAB; FRG1; NSMAF; USP39; DTYMK; PTOV1; LDHA; PSMD14; YBX1; NRD1; C2orf25; ATP5J2; ATP1A1; COX8A; HSD17B7; SPINT2; COX17; LRRC40; C16orf57; PSMD1; PCMT1; NUP93; NDUFB4; PTCD3; HADH; DDX39; NDUFA4; GMPS; METT11D1; NGRN; NFATC2IP; ANAPC13; hCG_1776980; TOMM70A; PATZ1; TRIM28; FTO; TDG; PCID2; TCP1; GSPT1; NDUFC2; TXNL4A; ARF4; CCDC53; RUFY1; DDX1; MAGOHB; MTX1; SAFB2; NUBP2; THOC5; ATF4; POLRMT; ZNF83; RANBP5; SLC25A44; DDX18; ZMYM2; C1orf41; PRPF19; POLR3E; DGCR8; C11orf10; IHPK2; PSMD2; SNX4; EID1; TMPO; LARP1; UNC50; HAX1; MAP2K2; NDUFS8; KIAA0999; TMED5; PREB; SUMO1; LARS2; WDR59; SNRPF; LOC730107; KHDRBS1; LSM3; GOT2; CUL4A; BOLA2; MTHFD2; NUP37; SF3B5; UBA5; NXT1; HK1; SHFM1; PSMD8; PRKRA; ATP5SL; FBXW2; C9orf16; BIRC2; TERF2IP; CCDC86; CHCHD3; C16orf80; ILF2; MRPL3; LSM5; GATAD2A; TUBA1C; PPP1CC; RSAD1; DPP3; TCEB1P; NIT2; CTR9; HIBCH; SAMM50; GARS; WDR82; ACTL6A; MYOD1; CEP63; SERP1; LSM1; METTL5; SRPK1; DYNC1H1; ATP5G3; PIN1; INPP4A; C20orf24; TCEB1; PRUNE; DLG1; CBX3; SAC3D1; NDUFS6; IKBKAP; SLC25A46; UBA2; TTC27; MRPL9; PHF20; MEA1; BZW1; MPHOSPH10; CALM2; MRPL16; HDAC1; ERCC5; OSBP; CRY1; SCP2; TSPYL4; EPM2AIP1; AMD1; MDH1; GORASP2; CCBL2; CLEC3B; DBF4; GPR89B; UBL5; VPS8; MSL2L1; DECR1; NOL11; NDUFA6; NDUFA7; AOF2; COX7C; EIF3M; GSS; TMOD1; FBL; MDM1; CDC16; JARID2; DGUOK; PSMC2; RTN4; POLR2H; METTL9; CUTA; COX6C; TAF2; GCDH; GPR89A; TRIM33; EFTUD1; PSMB2; DOCK2; PPM1A; ADA; VAPA; UBAP2; MRPL48; TUBA1A; IDH2; SSR2; SNRPD2; NDUFB6; STAU1; VDAC3; LETM1; SPECC1L; MRPL13; SMARCAL1; TRIM37; MSH2; SLC2A3P1; ANP32B; ALG9; MIF; ATP13A3; THEM2; KIAA0494; C16orf61; NDUFA13; RPIA; PRR14; ITGAE; CLNS1A; CDC25B; RTN3; KIAA0241; NDUFA3; C19orf53; ZC3H13; SEC61G; TFG; C11orf48; SPAST; UFD1L; FBXO46; CDR2; NCOR2; EXOSC8; MTMR6; HINT1; SLC3A2; ATF2; ATMIN; ZDHHC4; LEPROTL1; ADH5; SLC25A38; PCM1; HMG2L1; MRP63; ST13; HYOU1; ATIC; UBR4; AACS; GMDS; FAF1; CNOT7; C11orf51; PMF1; MTMR2; DRAP1; COX11; KIAA0152; INTS9; SEC61B; LDHB;

Suppl. Table 3 – page 22

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

FADS1; ABCD3; DCUN1D1; GRSF1; LCMT1; DNAJC9; RAD21; FADS2; NUP50; TFPT; SFI1; FDPS; C11orf49; THYN1; LSM4; KIFAP3; SSBP3; FDFT1; RCN1; CLPP; PTP4A2; SLC1A4; CD47; LANCL1; EXTL2; SEMA4D; CDK5RAP3; AGL; C9orf78; NUCB2; HMGCS1 PTGES3; IQGAP2; MYC; PRPS2; CD44; C15orf39; CASP1; C11orf24; ANXA2; MSL3L1; CTNND1; NAGPA; NDRG1; DYRK4; S100A4; ALDH3B1; GPM6B; CLASP1; CHD9; ZNF672; DBN1; NUP205; SEPHS1; TMCC1; GYS1; FOXO1; GTF2IRD1; FAM65A; CUX1; ITPR3; SMARCA4; HMG20A; RICS; RNF31; TXNRD1; DNMT3A; ZDHHC3; VAV1; EIF2AK3; ZNF91; KNTC1; NARFL; WASF2; RASA4; LBA1; SCARB1; RY1; PTP4A3; NRN1; ARHGAP29; TNFRSF21; TEL-AML1 SMARCA4 <0.001 0 + up 400 54 ABHD3; TCFL5; TNS1 TSPAN32; S100A4; MLC1; GREM1; LGALS1; CCPG1; LTBR; CCNA1; MATK; MAP3K5; ATP8B4; MGST2; SERPINB1; ABHD4; NLRP3; CD302; MYO1F; MAP7; ARTN; PTGES3; HK2; SFXN3; ORC2L; ZNF107; ZNF273; ZNF43; ANP32E; CCR SMARCA4 <0.001 0 + down 1000 29 ZNF675; DBN1 CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; HLA-DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; VPREB3; JUP; POU2AF1; IGHM; CHD7; TCF4; HLA-DQB1; INSR; GGA2; EGLN1; LAPTM5; PTPN18; HLA-DRB6; BACH2; GNG7; tcag7.1314; FLJ20674; LARGE; 3.8-1; FADS3; FAM65A; HLA-DOA; ERO1LB; FOXO1; GTF2IRD1; C10orf10; NEIL1; MYO5C; ALDH3A2; GAB1; MDM2; VIPR1; RAI14; SSH3; LDHB; DCUN1D1; SMARCAL GRSF1; LCMT1; RAD21; NUP50; ETFB; FDPS; SLC25A20; THYN1; LSM4; TXN; T-ALL 1 <0.001 0 + up 400 67 RCN1; CD47; LANCL1; IMPA1; SEMA4D; FAH; C9orf78 VAV3; EML4; ABCC4; GPATCH2; EWSR1; KIAA0564; PIGB; PLCB1; GCLC; ELF1; PDE8A; TPD52; STAM2; RPS6KA2; SENP7; MCTP2; LRRC8B; E2F5; PCDH9; FPGT; DENND4A; PRKACB; GLS; CD84; C20orf30; MAGED4B; CST3; SAMSN1; SLC46A3; C9orf45; RHOBTB3; PAM; FCGR3B; ZNF364; HIPK1; CBLB; DLEU1; MINA; BTG1; MRPL35; TNFRSF21; NIPSNAP3B; ENPP4; AGPS; TMEM38B; GIMAP6; PTPRD; TCL6; SERPINA1; PIK3R1; GNS; APC; FADS3; MARCH7; TES; PIP5K1B; NUDT4; F11R; GIMAP5; SLC7A5P1; C10orf6; RBMX2; DEK; NDUFA1; PSMG2; SMS; USP11; PTP4A1; E2F3; CBARA1; SGCB; C4orf27; RANBP9; DKC1; SAP30BP; CCT8; ATP5J; FANCE; STX8; PGRMC1; BDH2; UXT; MID1IP1; KIF4A; C11orf67; VBP1; WRB; MORF4L2; ING2; CANT1; SSR1; UBL4A; TBC1D25; PIP4K2B; C10orf119; HMGB3; FBXO9; PRPS2; PRPS1; PSMG1; RBBP7; CASP7; HMG4L; BAG5; SLC43A3; PHF10; ZMYM3; VRK1; ARMCX6; TBP; C21orf45; FMR1; PHF3; EBP; PARP2; NGDN; KDSR; TK1; CCDC22; RPL10L; ZNF673; LOC390183; MCTS1; ERCC6L; GLA; HMGN1; C21orf66; PGK1; SUMO3; SLC35A2; DONSON; NDUFB11; F8A1; BRCC3; Hyperdip>5 NSDHL; DYRK1A; SUV39H1; RAB9A; PRDX4; PDHA1; ZBED1; HDAC6; 0 SUV39H1 <0.001 0 + up 1000 188 UCHL5IP; M-RIP; CETN2; ORC3L; WDR7; TIMM17B; STAG2; HUWE1; MTMR1;

Suppl. Table 3 – page 23

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PHKA2; PIN4; ACOT2; SLC19A1; CHAF1B; PQBP1; ARMCX5; MPP1; POLA1; GSPT2; UBE2A; MAGEH1; LAS1L; RRP1B; MGC39900; GPKOW; HNRPH2; SOD1; UBQLN2; SLC9A6; FTSJ1; USP9X; ARMCX1; RNF113A; MED12; MTCP1; DHRS4; RP6-213H19.1; PSMD10; TCEAL1; HCCS; GPRASP1; SCML2; TCEAL4; C14orf147; UPF3B; MORC4 AHNAK; BAALC; SECTM1; CDC42EP3; PDE8A; GBP2; FOXP1; KLF7; SLC35D2; CCR SUV39H1 <0.001 0 + up 750 17 MKI67; HJURP; ARHGAP19; MCM10; TOP2A; MAGED1; ANP32E; HMG4L CD74; HLA-DRA; HLA-DRB1; PAX5; CD19; BLNK; HLA-DPA1; C14orf139; HLA- DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; CD24; TCL1A; BTK; CD79A; VPREB3; JUP; PLCG2; CIITA; NCF4; POU2AF1; TFEB; IGHM; CHD7; GALNAC4S-6ST; RIPK2; TCF4; HLA-DQB1; INSR; HLX; STX7; SLC27A3; EGLN1; LAPTM5; PTPN18; LAT2; HLA-DMB; BANK1; STX3; HLA-DRB6; PFTK1; CD9; PTPRE; BACH2; HCP5; GNG7; PTK2; RHBDF2; LILRA6; LILRA2; TRIM38; ENG; HLA-B; TLR1; tcag7.1314; FLJ20674; HLA-F; FHL1; PDLIM1; KIAA0040; STK32B; LILRB1; CSDA; SOCS2; LARGE; NLRP1; 3.8-1; FADS3; RGL1; ADCY6; PDE4B; FAM65A; LY86; TULP4; ADCY9; C17orf60; KCTD15; HLA-DOA; ERO1LB; UNC119; VPREB1; CTGF; HIST2H2AA3; HLA-J; GALNT14; CIDEB; SCML2; C1orf38; HLA-G; SCARF1; MBP; SPINT1; S100A13; DENND3; C10orf10; NEIL1; CRIM1; MYO5C; ALDH3A2; GAB1; P4HA2; LRRK1; MDM2; SLC35D2; VIPR1; ELK3; LILRB2; WFS1; IRF8; CPM; OGFRL1; ECHDC3; BTN2A2; LILRB3; TSC22D3; RAI14; ARSD; KMO; SSH3; FES; GNA11; TCL6; MME; NPR1; KIF13A; SLC35E3; MYLK; IL1B; FAM50B; CAST; TRMT12; HLA- DRB3; SPIB; MYLIP; TERF2; BCAR3; RAB13; NCF1; PIP5K1B; RAPGEF3; DRAM; KLHL2; TAP2; GNAI1; CD180; SLC2A5; TPST1; LDLRAP1; DIP2C; PPFIBP1; DRP2; DACT1; KANK2; ARHGEF12; HHEX; S100A1; C14orf113; C14orf132; STAG3; PHACTR1; TLR2; CELSR1; IRF7; LDOC1; HIST1H2BF; SYT11; COL5A1; HLA-DOB; SCHIP1; CORO2B; NUAK2; DGCR6; SLC16A2; OR2A9P; HIST1H2BG; IRF6; C12orf49; F13A1; CYP2B7P1; UNC93B1; OCA2; HLA-DQA1; ALOX5; PDK1; LIMD1; PCDH9; RNF19B; SERPINI2; EGFL7; ZNF193; ABCB4; FGD2; CYBB; ADRBK1; SMAD3; PCSK6; CRTAP; HIP1; ECM1; ACTR2; HLA-A; GSTM5; NAV1; MGC5370; SH2B2; PRO2268; UNC13B; PDE8B; CCR1; NCF2; BMPR2; STAT2; ELL3; RIN2; MTSS1; C9orf167; SGSH; C9orf45; SPPL2B; LTB4R; EMP2; CBR1; BMP2; RASL10A; ENTPD1; FGD1; P2RY14; CDC25C; SAMD4A; JAM2; HIST1H3D; CCDC81; KHDRBS3; SSX4; NRGN; HLA- DRB4; GABBR1; PBX2; DUSP3; KCNA5; ODZ4; GPR132; SERHL2; HIST1H2BE; CAP2; HIST1H2BN; IGSF3; DSP; OR1A1; MRC1; NOL4; IFIT3; OLFML2A; LTBP2; FLT3; TBXA2R; FOXP1; OR7A5; CEACAM21; ENTPD3; SEMA5A; LTBR; MS4A1; CD86; CXCR6; SEMA6D; CD40; TBC1D9; EPHB3; IFIT2; ELOVL2; BACE1; ATP10B; SLC11A1; HIST1H2AM; CSHL1; NLRP2; HIST1H2AJ; GAS8; T-ALL CBX3 <0.001 0 + up 1500 608 EFNB1; ADAM19; HIST1H1C; HSPA2; HOMER2; IL8; SPRY4; IL13RA1; TP53I11;

Suppl. Table 3 – page 24

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

ASB13; PTPRG; DDR1; SEMA3F; NEBL; C5orf4; ADCK2; HIST1H4H; FLJ20489; RHOQ; ULK2; FER1L3; ZNF467; SLC17A7; LDB2; CKMT2; ANKRD55; REEP1; ITGA5; LOH3CR2A; IL3RA; KIAA0774; ECM2; KIAA0746; CYP2B6; C10orf56; KCNJ2; HIST1H2BI; FKSG49; MYO10; DPEP1; TXNIP; MUC5AC; IRAK3; SH2D3C; USP10; EPHA7; GJC1; MGP; MLPH; ITIH4; IFI30; C6orf145; RBM47; UGCG; TGFB1I1; GIMAP4; BC37295_3; ZNF117; SIGLEC15; UTRN; EGFR; CLEC4E; AK5; PLVAP; FERMT1; NFATC4; OPHN1; STARD13; FLT1; SP4; TCL1B; TNFSF13; ALDH3B1; KCNMB1; SEMA6A; KIF1B; SAMHD1; AQP1; SUOX; IGKV1OR2-108; PTGS1; CD52; ERBB2; MS4A6A; EVC; LILRB4; DKK1; HAP1; RBMS3; LRRC17; SCN1B; LRRC40; ZNF146; PSMD1; PCMT1; NUP93; NDUFB4; PTCD3; HADH; DDX39; NDUFA4; SMC3; METT11D1; NGRN; ANAPC13; hCG_1776980; TOMM70A; PATZ1; TRIM28; RAB5A; SACM1L; TDG; TMEM208; PCID2; TCP1; ARMC1; NDUFC2; TXNL4A; ARF4; CCDC53; DDX1; MAGOHB; MTX1; SAFB2; THOC5; ATF4; RANBP5; DDX18; UBR5; ZMYM2; C1orf41; PRPF19; POLR3E; DGCR8; C11orf10; IHPK2; PSMD2; SNX4; EID1; TMPO; LARP1; UNC50; UQCR; NDUFS8; PREB; SUMO1; SNRPF; LOC730107; KHDRBS1; LSM3; GOT2; CUL4A; BOLA2; NUP37; SF3B5; NXT1; STMN1; SHFM1; PSMD8; PRKRA; ATP5SL; FBXW2; SLC39A6; BIRC2; TERF2IP; CHCHD3; C16orf80; ILF2; MRPL3; LSM5; GATAD2A; TUBA1C; PPP1CC; TCEB1P; CTR9; MLF1IP; HIBCH; SAMM50; GARS; WDR82; ACTL6A; MYOD1; SERP1; LBR; LSM1; METTL5; RFXANK; SRPK1; DYNC1H1; ATP5G3; PIN1; C20orf24; TCEB1; PRUNE; CBX3; SAC3D1; NDUFS6; IKBKAP; SLC25A46; TMEM14A; UBA2; MRPL9; UNG; PHF20; SUB1; BZW1; CALM2; MRPL16; HDAC1; SCP2; TSPYL4; EPM2AIP1; MDH1; NOLA1; GORASP2; CLEC3B; DBF4; GPR89B; UBL5; KEAP1; MSL2L1; DECR1; PAICS; NOL11; NDUFA6; NDUFA7; AOF2; COX7C; EIF3M; TMOD1; OXSR1; FBL; MDM1; DGUOK; PSMC2; RTN4; POLR2H; METTL9; CUTA; COX6C; TAF2; RFC3; GCDH; GPR89A; TRIM33; EFTUD1; PSMB2; VAPA; UBAP2; MRPL48; TUBA1A; IDH2; SSR2; SNRPD2; NDUFB6; HLTF; STAU1; VDAC3; SPECC1L; MRPL13; TRIM37; MSH2; SLC2A3P1; C5orf13; ANP32B; MIF; ATP13A3; THEM2; UBE2V2; KIAA0494; C16orf61; NDUFA13; RPIA; CLNS1A; KIAA0241; ZBED4; NDUFA3; C19orf53; ZC3H13; SEC61G; TFG; C11orf48; SPAST; UFD1L; EXOSC8; MTMR6; ATF2; ATMIN; ZDHHC4; LEPROTL1; ADH5; SLC25A38; PCM1; HMG2L1; MRP63; GTF3A; ST13; ATIC; UBR4; FAF1; CNOT7; C1orf174; C11orf51; PMF1; COX11; KIAA0152; SIVA1; INTS9; SEC61B; LDHB; DCUN1D1; GRSF1; LCMT1; DNAJC9; RAD21; NUP50; TFPT; FDPS; LSM4; PTP4A2; CD47; LANCL1; SEMA4D; MLLT11; C9orf78; C14orf135; NUCB2 CD74; HLA-DRA; HLA-DRB1; CD19; BLNK; HLA-DPA1; HLA-DPB1; HLA-DMA; HLA-DRB5; CD79B; CD79A; SNX2; JUP; CHD7; GALNAC4S-6ST; RIPK2; HLX; T-ALL CBX1 <0.001 0 + up 400 93 INPP5D; STX7; SLC27A3; EGLN1; PTPN18; LAT2; BANK1; TSPAN13; STX3;

Suppl. Table 3 – page 25

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

ENG; TLR1; GAB2; CDK9; PDLIM1; STK32B; CSDA; SOCS2; LARGE; ADCY6; PDE4B; HIST2H2AA3; CLCC1; CIDEB; C1orf38; S100A13; DENND3; C10orf10; MYO5C; GAB1; GPX1; LRRK1; MDM2; SYNGR1; SLC35D2; ELK3; OGFRL1; ECHDC3; LILRB3; CAPN3; SSH3; SCARB2; SIVA1; RAP1GDS1; SEC61B; HDAC4; DNAJC9; PKIA; RAD21; RASGRP1; NUP50; TNFAIP8; FDPS; C11orf49; SLC25A20; THYN1; KCTD9; LSM4; HN1; SRPK2; ECT2; ELOVL5; ARL4C; PAFAH1B3; PTP4A2; INSIG1; MLLT11; VAT1; LZTFL1; NUCB2; HMGCS1; STAU2; NBR1; LAT; BCL11B; LCK; SCD MGC29506; CD52; MYO5C; ZSCAN18; EXDL2; SV2A; SERPINB9; DNTT; TNFRSF14; PHF15; ZNF135; GFOD1; ALOX5; ITGA5; NEDD4; SCHIP1; C11orf75; IL1B; DUSP26; ID3; ARMCX2; GIMAP4; DAB2; MYO1B; YES1; FGD1; NAV1; RYK; tcag7.1314; ZNF467; SUOX; CASK; SETBP1; MGC5370; EFNA1; RGL1; PRO2268; SALL2; PLCH1; GPR56; ZNF667; TREML2; SPAG16; CEP68; GIMAP6; RAPGEF3; C10orf10; CCND2; PECAM1; C6orf32; ITGA6; DAPK1; RSBN1; LST1; SERPINB6; A2M; CS; BCL7A; M6PRBP1; DGKD; GLT25D1; TBCC; TBC1D9B; APEH; EP400; MYH9; GMIP; RAP2A; GLUD1; CLASP2; BCAT1; ZNF394; MAP4; MLL CBX4 <0.001 0.02215 + up 400 81 ASXL1; SIRT7; IDUA; PRKCE; ZEB2; CHPT1; C1orf164; RHOBTB3 TSPAN32; CCPG1; CDC42EP3; GBP2; KLF7; SLC35D2; MKI67; TMEM48; CCR CBX5 0.002 0 + down 1000 12 HJURP; MCM10; TOP2A; ANP32E OR7E38P; RAG2; DALRD3; EWSR1; EPB41L2; AEBP1; NCKAP1L; BCL2L1; CD38; AKAP12; FAAH; HPS4; SYK; MCTP2; E2F5; PCDH9; RHOBTB1; CD84; VEGFB; TUSC2; CST3; ARNTL2; IL7R; NME3; DIP2C; FCGR3B; HIPK1; ZNF124; PRKAB1; ALDH4A1; MT1E; KCNMB3; SGSM3; ORAI2; LOC91316; NKTR; FLJ13769; MAZ; TM9SF1; OGT; SLC35A1; PRPS1; RBBP7; BAG5; C4orf15; C4orf41; BACH1; LAMP2; FMR1; PHF3; SIRT1; ACSL4; NGDN; RDH11; MCTS1; LMBRD1; HMGN1; VPS26A; ALDH6A1; USP16; VAMP7; PGK1; SUMO3; DYRK1A; MSN; TTC3; MARCH5; SFRS15; PDHA1; SH3BGRL; HDAC6; WDR7; UBL3; STAG2; HUWE1; TMEM164; CPD; CUL4B; ARMCX5; RBPJ; POLA1; C21orf33; CXorf45; ATP6AP2; MAGEH1; LAS1L; RRP1B; MORC3; HNRPH2; Hyperdip>5 ABCB7; UBQLN2; CYB5A; PHB; FTSJ1; USP9X; RNF113A; PIGP; RP6-213H19.1; 0 MYST2 <0.001 0.04189 + up 750 100 PSMD10; UPF3B ADK; PTGES3; SORD; AKAP1; GPX7; IQGAP2; C22orf9; ATP13A2; MYC; PRPS2; ACVR1B; KIAA0564; GALNT2; PUS7; CD44; PTGER4; UCK2; MINA; NOL14; ITM2C; CCDC86; RRS1; AP1S2; C15orf39; DIAPH2; C11orf24; LPXN; ANXA2; DPH4; PKIG; NUP210; EIF4EBP1; IMPA2; VIM; DKFZp667G2110; ZBTB24; MPZL1; CTNND1; ZNF593; PCBD1; SYNJ2; MT1X; FLJ11184; CDKN2D; MAPKBP1; MT1L; POLR3D; CCDC69; FAM98A; MGST3; NIP7; NRXN2; ZMAT3; CTSC; CIB1; FXN; MT1H; ASAHL; PTPN6; TTLL12; NCF1; FAM53B; PUS1; NFATC1; INPP1; CCDC94; SMPD2; TAGLN2; MT1P2; S100A4; FCHO1; BCAT1; TEL-AML1 MYST3 0.004 0 + up 2500 558 C9orf16; BNIP1; MT2A; ANXA2P2; GRAMD4; LRMP; ALDH3B1; PPAT; PBX3;

Suppl. Table 3 – page 26

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

ENDOD1; IPO4; APOLD1; ABCB4; C12orf44; CD96; FABP5; GPM6B; FAIM; KLHL21; GLUD1; VPREB1; CSRP1; MT1G; CXorf21; CLEC11A; NLE1; RRBP1; EXOSC5; STS; PDLIM1; FASN; CLEC2D; FAM26B; RHBDF2; TMEM121; GLRX2; RPL27; LIMD2; SCPEP1; HDAC9; TRIB2; CD86; LDLRAP1; DET1; TERT; XYLT1; ME3; SERPINB8; NR1H2; LOC92482; MT1F; TREX1; MAP3K1; SYT11; TLR2; CHST6; IGFBP7; ATP1A3; NR1D2; PTER; CCDC81; P2RX5; AHR; SCO2; GRB2; SAMD4A; TNK2; FLNA; ARL2; BOP1; RIMS3; YWHAE; MATK; TBC1D8; BSPRY; ABCB1; VDR; IL17RA; KLHL2; RNF24; GTPBP3; LYN; RPS6KA1; C12orf10; ADARB1; DCPS; C20orf27; BIK; SEMA4A; ARF6; CD248; C11orf21; XTP3TPA; MKL1; RPP40; LTK; BLK; LOC391132; DAK; C21orf91; ENC1; MT1E; CD320; OGG1; SPARC; PLGLB1; dJ222E13.2; EMR2; KANK1; LRRFIP2; SIT1; LGALS1; GSTM4; TRPV2; MRPL12; APEH; CAST; CPM; NUAK2; RCC1; CD48; EHD4; RHOQ; BCL6; SPIB; CLN5; SPON2; RABIF; HCRP1; HK2; IQSEC1; CD9; TSPAN32; PLCB1; NP; CD84; LOC100137047-PLA2G4B; RBM47; SCLY; ECHDC2; ARHGEF11; KCNA3; JARID1C; DOK1; FAM125B; QTRT1; ALCAM; CTNNBL1; FRAT2; PDGFA; MS4A6A; PPCDC; ENDOG; TSEN34; CTSO; SIDT2; SETD6; EXOC7; MRTO4; GLDC; FOSL2; S100A10; PLXNC1; ATP2B1; C6orf62; RANGAP1; SLC29A1; PTGES2; RPS11; MYT1L; H6PD; EAF2; TBX21; RIN2; VNN2; GLT25D1; APOBEC3F; BAG2; SET; ARPC4; NLRP3; FAM30A; FGR; RPL27A; TMEM106B; SPPL2B; PRKCD; KIAA0125; MAN2B1; RGS16; RAP2A; CCDC14; CENPB; IL13RA1; KLRK1; CSF1R; RNASE6; ANXA6; C9orf9; NAGLU; TRIM8; QPRT; COL4A3BP; TUSC4; TNPO2; MBNL1; MXD4; SLC2A6; PYCR1; ITGB7; PIGB; ERP29; ITPKB; MPEG1; PRKCE; RHOB; ZNF239; DFNA5; PSCDBP; C14orf101; C20orf103; EIF2C3; RNF144A; KIF1B; CAMKK2; CTBP1; BDH1; SMAD3; CAV2; PPP2R1B; KLHL23; SNTB1; S100A11; OSBPL1A; CLEC7A; TPBG; HIP1; TBXA2R; SAMHD1; SLAMF1; DSCR3; ANGPT2; RRP9; FGF9; UST; LAMA2; LAT2; BLCAP; FAM60A; RNASEN; ZMYND11; AARS; ATP2B4; MCFD2; DNAJA1; POMT1; UBE3C; CCNL2; BTN3A1; CLINT1; ADNP; FUT1; MGC29506; SIN3B; C1RL; RBM5; WSB2; SYNJ1; PCAF; ZNF12; CCNT2; ZKSCAN1; CTDSP2; PSME4; SNAP23; STAT5B; ZMYM3; RNF38; PPP1R12A; PEX19; PHF2; FLJ10404; EIF1B; LGALS8; RING1; POLB; C11orf75; NIT1; YTHDF1; C20orf11; LUC7L; TCF7L2; HECA; DNAJB4; ZNF675; DNAJC10; DMXL2; ZCCHC8; FLJ10213; KIAA0174; CALM3; UBE2I; PQLC1; ITGB1BP1; NARF; H2AFV; RUFY3; PHTF1; RSBN1; HNRNPA0; ZMYM1; PUM1; SETD1B; MAN1A1; ZMYM2; RAB3GAP1; ZNF273; MAGED2; TLOC1; LAPTM4A; SH3TC1; SNRPN; ZNF43; CRKL; KBTBD2; C12orf35; CHD1; RAB1A; NT5C2; IFRG15; POLS; MAPK6; C1orf165; SCMH1; MYST4; RSRC2; YTHDC2; RAP2C; GDI1; MSRB2; KIAA0265; RYK; PCGF3; PVRIG; WDR37; MECP2; IPW; ZNF281; KIAA0515; SSBP2; GTF2E1; BRD1; TNKS; KIAA0317; MRPL49; NASP; SPTBN1; PBXIP1; SFRS8; GOLGA8A; UPF2; PRKX; PRKACA; C10orf18; STMN1; PHF1;

Suppl. Table 3 – page 27

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

BNIP3L; FOXK2; PIP5K1C; CREBBP; PPM1B; SPTAN1; MAPK14; HRB; ACSF2; RIT1; RHOF; YES1; PATZ1; ARFIP1; POU2F1; RAB22A; HIST1H2BD; ZMIZ1; MTF2; ZNF107; NBPF1; N4BP1; CAB39; ALDH5A1; GAK; MYST3; RBMS1; TRAF5; CLSTN1; OXSR1; YEATS2; DCP2; PLCG1; KIAA0232; BTBD3; CD200; DPYSL2; CCDC93; PARC; SRBD1; MAP4K3; ACSL3; ARHGEF18; REL; WSB1; ENTPD4; MAPK8IP3; RAPGEF2; FBXW7; ZNF217; CLASP1; CHD9; CENTB2; JMJD2B; POLE; NUP205; SEPHS1; PLCL2; MLXIP; SERINC5; VAMP5; FAM134B; FHIT; LEMD3; TMCC1; FAM50A; B4GALT6; SLC35E3; CUX1; AIF1; MKL2; GNPTAB; INTS3; PIK3IP1; ABHD10; SMARCA4; SETD4; UBE2E3; FCGRT; GRINA; FKBP1A; HMG20A; ISG20; BMP2; NMT2; ELK3; ITPR1; TRIM24; RNF31; TXNRD1; FYB; ZDHHC3; VGLL4; EDEM1; RECK; PRKCB1; VAV1; EIF2AK3; ZNF91; CHCHD7; WASF2; RASA4; RY1; SPTA1; ENPP4; CYB5R2; WDFY3; PCCA; DSG2; C13orf18; IDI1; FUCA1; FCHSD2; CBFA2T3; PIK3C3; NR3C2; ARHGAP29; ABHD3; TCFL5; C10orf26 NDUFA1; PSMA7; MRPL34; COPS3; COX6C; COX7B; FRG1; RBBP7; PSMC5; PSMB3; UBE2A; ATP5J; UCRC; TIMM8B; ARPC5; ENSA; MAPBPIP; SLC25A5; NDUFB8; EEF1E1; ATP5G1; EIF4A3; NDUFS6; RAN; COX6A1; SFRS2B; PSMD2; SF3B5; PGAM1; IQGAP1; MDH1; NDUFS1; PSMA3; HSPA5; MCTP2; TP53TG3; CCR5; APOL6; GRIK2; MXI1; RASL10A; EGFL7; KAL1; AKAP12; GNG11; FLRT3; EFR3B; PRKG2; ZNF239; ZNF192; CSHL1; CDH11; REEP1; FLT1; Normal MBD2 <0.001 0 - up 1500 63 PCDH9; PCBP4; FER1L3; SLC6A16; AGMAT; PBX2; TXNRD3; MPPED2; HEY2 MSN; CTDSP2; LASP1; AMZ2; OGT; TMED10; CNDP2; SAPS2; MORC3; PLEKHM1; C14orf1; SEL1L; UBE4A; EXOC1; CSNK1D; PPP2CB; C14orf159; GMFB; KIAA1109; FAM134C; SFRS18; RPN2; CLINT1; CRLF3; ATP6AP2; UBE2D3; LAMP2; POFUT2; PAFAH1B1; UNC50; RPL17; RP6-213H19.1; ARL8B; SSR4; WSB1; SERINC1; ZNF706; TM9SF1; GMPR2; TMEM131; ZMYM4; GOLGA5; TMEM59; RUVBL1; C3orf63; HELZ; ZDHHC7; MAPK14; MCM3AP; RHOT1; HERC1; TMEM41B; CMTM6; GLOD4; UBR2; CUL5; LAMP1; ISCU; RNF111; VTI1B; PGK1; SFRS17A; SLC38A2; FOXJ3; SPTLC1; BTAF1; YIPF6; UBR4; NCOA4; NT5C2; SMCHD1; SNX1; MRFAP1L1; FRYL; UXT; GAK; PIGG; RBL2; KIDINS220; TRIM33; LRRC47; ACTR10; GGNBP2; MAPRE2; ROCK1; WDR37; PCGF3; KIAA0907; NUDT9; ZKSCAN1; CDIPT; UBE2Z; ZFAND6; CXorf45; C19orf56; SFRS5; RNASEN; C5orf15; PAPOLA; MDN1; C21orf66; VPS26A; TMEM1; RAB6A; ATRX; LRRC37A4; DENR; EIF4A2; ASF1A; PIP4K2B; NDUFB11; PPT1; ZNF451; GALNT7; DCN; PI4KAP1; VAMP7; MTCH1; RNMT; DCK; THOC2; CRYZL1; RAB7A; CUL4B; RAB6C; C21orf33; SLC9A6; METAP1; SPAG7; PNN; DCTN2; DERL2; SDF2; DDX3X; HNRPA3P1; GPATCH8; MSL-1; PDHA1; COX15; ANKRD49; SEC63; TTC3; ADAR; ZDHHC6; METT11D1; ZNF574; PARP6; LMBRD1; PHF8; IRAK1BP1; TLK1; PCNT; MPHOSPH9; E2A-PBX1 MBD1 <0.001 0 - down 1500 343 HNRPH3; METTL3; SPEN; MAN1A2; TINAGL1; SLC22A5; ADCK2; PLAC4;

Suppl. Table 3 – page 28

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

NEBL; HIST1H2BN; BSPRY; ARL4A; ZNF528; DDR1; ABCC4; ATP1A3; TMEM63A; TAT; KMO; OR7E38P; MYOZ2; TCL6; COL1A1; PARD6A; C6orf60; SLC35F5; NCF1; MPP6; ANKRD55; VIPR2; RGS5; BCL9; EPAS1; UCK2; ERO1LB; CDC14B; E2F2; SEMA6D; RASIP1; KCTD20; MUC5AC; CD24; FADS3; TPR; PLGLB2; NR1D2; PHLDA2; ENTPD3; BCAS4; LRP4; PRL; CLEC2D; SPPL2B; AKAP12; SORT1; PCSK6; CPM; GJC1; RGS2; FLJ13769; SLFN12; MLPH; C6orf124; AASS; KCNJ2; BASP1; KCNJ3; RHOQ; SNTB2; IL8; CD84; FERMT1; CD48; PIP5K1B; SEMA5A; MDM4; PCSK5; CD72; PAX5; PLS3; FLJ20674; PDE4D; ATRNL1; GLDC; TRAK2; GPATCH2; RBBP5; KRAS; ADAM19; TRIM16; C1orf135; NFATC4; BMPR2; CELSR2; RAG2; ARHGAP8; TTC9; ST6GALNAC4; ITPKB; ZNF124; ARHGEF11; CSRP1; TCF3; SPAG6; SORBS2; MYT1L; MYL4; JAM2; PAWR; IGHM; GATM; SH3PXD2A; PPFIBP1; KCNJ16; TNK2; BIK; FAM152A; EPB41L2; VDR; TMSL8; EMP2; BACH2; NRGN; PRR5; CORO2B; PPFIA4; ARNTL2; SRGAP2; MAP3K1; PHACTR1; SH3BP4; EWSR1; F13A1; LTBP2; DOCK9; RHOBTB1; CASC1; TRIB2; TGFBR2; MAP1B; GPR176; PSAT1; PIGZ; ODZ4; ENDOD1; D4S234E; QRSL1; GNAZ; KCNA3; FNDC3B; ALDH1A1; GALNT14; SYT1; TMEM121; DOCK10; CALD1; RASAL1; ELOVL2; CCDC81; IL12RB2; IGSF3; APBB2; KCNMB3; ELL3; BLK; IRF4; KIAA1305; AOX1; ROR1; SAMD4A; LRMP; KANK1; ADARB1; DACT1; KCNJ12; FAT; FHOD3; SORBS1; SEMA4C; SLAMF1; GP5; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; SLC27A2; MERTK; PBX1 PRDX3; NDUFA1; TRMT5; COPS3; COX7B; FRG1; HMGN2; RBBP7; PSMC5; UBE2A; ATPIF1; ATP5J; HMGN1; UCRC; FLII; SOD1; RCOR1; HMGN3; AHSA1; PECI; CCDC56; EIF4A3; RWDD1; PSMD2; SF3B5; SLC9A6; PHB; PSMA3; NDUFA8; MCTP2; GPHN; TP53TG3; CCR5; APOL6; GRIK2; CBLB; RASL10A; PDE8B; TOX3; KAL1; HIP1; AKAP12; FLRT3; EFR3B; PRKG2; ZNF239; CD84; ZNF192; CSHL1; CDH11; ANGPT2; REEP1; RAG2; LRRC8B; PCDH9; PCBP4; GLDC; FER1L3; SLC6A16; AGMAT; TXNRD3; MPPED2; HEY2; LHFPL2; CHST7; Normal MBD1 <0.001 0.05189 - down 1500 69 CHST2; STAP1; PTPRM; CENTG2 C4orf41; SIRT1; RRAGA; NUP54; RAB5A; CD46; PSMC6; COPS4; LAMP2; TCEAL1; HNRPH2; NDUFB8; PIN4; BZRAP1; GRIK5; SSH3; ATP1A3; ANXA4; CTNS; E2F2; ERBB2; GPR176; SH2B2; PCDH9; CXCR3; DLGAP4; dJ222E13.2; Pseudodip MBD1 0.005 0 - down 2500 37 HCRP1; MPO; SERHL2; PYCR1; COL9A3; TAP2; AEBP1; SLIT2; PALM; SFRS6 IGF2R; RNF40; EFTUD1; ANP32A; EFHA1; HDAC1; THADA; MCRS1; H1FX; C1orf160; RER1; TH1L; TCF12; MAP2K2; YLPM1; RMND5A; HDGF; TMEM183A; ADAM17; GOLGA1; NGLY1; C13orf23; UPF1; PPME1; IQCC; DLEU2L; PSCD2; MPHOSPH8; ZNF131; TFG; MZF1; PMS2L8; DKFZP564O0523; DDA1; MSL2L1; ARID4B; BTBD2; IPO9; RHOT2; SR140; IL7R; GTPBP8; PCM1; Hyperdip>5 SFRS12; PMS2L3; MDM1; PMS2L1; RBBP4; ADNP; MCAM; PTCD3; MBD4; 0 MBD4 <0.001 0 - down 1000 257 UBE2N; SNRP70; PMS2L11; ZNF364; CLEC16A; HIPK1; C5orf5; VPS13A; IQCB1;

Suppl. Table 3 – page 29

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

SNRPA; PSMF1; NOL12; FBXL14; ARIH2; RFWD3; HP1BP3; GNB1; WNK1; ORAI2; LONP1; MYO9B; DCTN1; GTF2F1; IRF3; ATR; EDC4; RAB5B; NKTR; BRD4; MRPS31; PPM1G; ANKHD1; HNRPUL1; HTATIP; NSUN6; RABL2A; C12orf47; TWF1; FAM89B; ANAPC5; PRPF38B; TRIM28; PIK3R1; C1orf77; ZMYND8; KLF12; NDUFA3; PIN1; LOC389168; NDUFS8; PHKG2; CAPN1; ING3; MLH1; HNRNPU; ZNF44; LOC23117; SLC25A36; POLR2J4; STAB1; S100A13; IFI6; SCARF1; BANK1; LILRB2; LDOC1; KIAA0427; CCND2; IER3; SLC16A2; ST7; SGSH; BACE1; NOS2A; DAPK1; ULK2; NPR1; TREML2; SPRY4; SCN1B; LARGE; NEDD9; RIN2; C17orf86; IFI30; OAS2; HLA-DMB; BCL2L2; SYNJ2BP; OR2A9P; ECM2; CYB561; XAF1; HERC6; SLC35E3; TIE1; HCP5; HLA-F; DUSP3; ARSD; NEO1; VIPR1; OAS1; EPHA7; ZNF516; BCAR3; ELK3; NPY; NDST1; PLEK; NCF2; ZNF467; HLA-E; KIAA1462; SERPINB6; PRSS7; F2RL1; PDK3; TBC1D9; IGFBP4; ACSL5; TNFSF13; RGL1; FGD1; WDFY3; STYK1; TNFRSF10B; CD86; CLEC4E; RPL10L; ERG; PPM1F; DDX60; TMEM165; KIAA1166; EXDL2; IL1B; PPAP2B; FLT3; GSTA4; IRF9; MAGT1; OCRL; IFIT5; FAM49A; SPIN2B; KBTBD11; IFIT3; IFI44L; MRC1; H2AFY2; PDE4B; NGFR; TNNI2; GNA11; RRAGB; CD1C; PLVAP; LGMN; CPD; C10orf10; IFIT1; CIDEB; SIGLEC15; ASB9; OGFRL1; ENOX2; RBM47; PLCH1; PET112L; TLR2; CSF3R; ALOX5; CELSR1; SH3BP2; PRKAR2B; CYTL1; ECHDC3; ARHGEF10; PIP3-E; CYB5A; EFNB1; SETD3; PDXK; MX1; SETBP1; PIGP; LOC57228; ALDH3B1; LTB4R; DHRS4; CEBPE; SH3BP5; TCEAL1; ITSN1; MYBPC2; ACOT9; SCML2; MS4A6A; TCEAL4; C10orf56; IL13RA1; MORC4; IL3RA; ZNF185 UQCR; MED16; NCOR2; GPX4; CDC34; RPN2; TRMT1; NUCB1; VIPR1; SEMA5A; TLE1; KIF13A; LRRN2; FLJ20674; ALDH3A2; BMPR2; ARHGEF11; LOC90925; KLHL2; JAM2; IGHM; GATM; PPFIBP1; VDR; EMP2; BACH2; NRGN; KIAA0040; IL1B; CORO2B; PPFIA4; LTBP2; CASC1; MAP1B; SLC15A2; CSF2RB; ODZ4; FNDC3B; ALDH1A1; CALD1; RASAL1; ELOVL2; CCDC81; IGSF3; KCNMB3; ELL3; IRF4; AOX1; ROR1; SAMD4A; DACT1; KCNJ12; FAM3C; FHOD3; SLAMF1; GP5; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; E2A-PBX1 MBD3 <0.001 0 - down 500 64 MERTK; PBX1 LEPROT; MPG; ARL6IP5; GSTK1; STX12; MFSD1; FEZ2; MKI67; TCF4; HJURP; CCR BAZ2B <0.001 0 - down 750 16 COL1A1; TOP2A; EIF4EBP2; MAGED1; HMG4L; DBN1 KIAA0430; SNAP23; AKAP11; STX16; TTC31; SLC35E2; LETMD1; UBE4A; EXOC1; CSNK1D; UBE3B; FAM134C; TMEM189-UBE2V1; OS9; ZZZ3; UNC50; MBTPS1; IKBKB; ARL8B; WIPF1; GSTK1; HERC2P2; GMPR2; ARF3; TMEM131; ZMYM4; ATRN; WDR42A; JOSD3; R3HDM2; MBD3; C3orf63; ZDHHC7; CCBL2; RHOT1; CHD9; HERC1; POLRMT; TMEM41B; CMTM6; PIP5K3; MAP7D1; CUL5; RNF111; CCNT2; SCAMP1; PIGF; EZH1; ARHGAP1; FOXJ3; ZDHHC17; FNTA; SPTLC1; ST13; TXNDC14; UBR4; GPBP1L1; GTF3C3; OXA1L; NT5C2; RPL15; E2A-PBX1 SETDB1 <0.001 0 - down 1500 283 DOCK2; SNX1; ATP5D; TMEM39B; C1orf164; BICD2; PIGG; KIDINS220;

Suppl. Table 3 – page 30

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

TRIM33; LRRC47; MYT1; ACTR10; GGNBP2; VPS13C; KIAA0907; ZKSCAN1; CDIPT; UBE2Z; ZFAND6; SFRS5; RNASEN; PARP4; C5orf15; MDN1; KIAA0494; DENR; EIF4A2; C1orf63; DMTF1; TMEM87A; TAF1C; FOXK2; RNMT; CSNK2A2; RAB7A; RAB6C; DCTN2; C19orf60; ANAPC13; HNRPA3P1; GPATCH8; VKORC1; MSL-1; SCAMP3; GORASP2; METT11D1; PARP6; LASS2; NIF3L1; MPHOSPH9; TINAGL1; SLC22A5; ADCK2; DEPDC1; PLAC4; NEBL; HIST1H2BN; RALGPS2; BSPRY; ZNF528; DDR1; TAT; TPST1; KMO; MYOZ2; COL1A1; PARD6A; C6orf60; SLC35F5; ANKRD55; VIPR2; PXDN; CD9; ZNF669; ZNF257; RGS5; BAMBI; EPAS1; DEF8; C14orf132; CDC14B; E2F2; SEMA6D; RASIP1; KCTD20; MUC5AC; CD24; FADS3; TCF4; NR1D2; EGLN1; GINS4; ENTPD3; HIST1H4C; LRP4; PRL; VASH2; SPPL2B; AKAP12; SORT1; SPINT1; PCSK6; ITIH4; CPM; GJC1; MLPH; C6orf124; MYLK; AASS; TJP2; KCNJ2; RAI14; KCNJ3; SPA17; SNTB2; IL8; CD84; EXO1; FERMT1; VIPR1; SEMA5A; MDM4; PTTG3; PCSK5; LRIG1; TLE1; KIF13A; CKAP4; LRRN2; PLS3; FLJ20674; PDE4D; ALDH3A2; RHOB; ATRNL1; RHBDL2; CD59; TRAK2; ADAM19; TRIM16; C1orf135; NFATC4; BMPR2; TTC9; COBL; ARHGEF11; ZNF385D; KLHL2; SPAG6; SORBS2; MYT1L; MYL4; JAM2; PAWR; GATM; ARL4C; SH3PXD2A; PPFIBP1; KCNJ16; TNK2; VDR; TMSL8; EMP2; P4HA2; NRGN; IL1B; CORO2B; PPFIA4; ARNTL2; SRGAP2; MAP3K1; PHACTR1; SH3BP4; F13A1; LTBP2; DOCK9; CASC1; MAP1B; FGF9; GPR176; PSAT1; ODZ4; D4S234E; GNAZ; KCNA3; FNDC3B; ALDH1A1; GALNT14; TMEM121; CALD1; RASAL1; ELOVL2; CCDC81; IL12RB2; IGSF3; KCNMB3; ELL3; BLK; IRF4; AOX1; ROR1; SAMD4A; KANK1; ADARB1; DACT1; KCNJ12; FAT; NCAPD3; NP; FHOD3; SORBS1; SLAMF1; GP5; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; SLC27A2; MERTK; PBX1 NUCKS1; TRMT5; KIAA0101; TYMS; RBX1; HMGN2; CDC2; CCNB2; TUBA1C; MCM6; RPA3; RFC4; H2AFZ; NDUFA6; CBX5; TOP2A; ARL6IP1; CKS1B; RAN; SFRS2B; PSMD2; TUBB2C; TP53TG3; CCR5; GRIK2; PDE8B; TOX3; KAL1; EFR3B; PRKG2; ZNF239; CSHL1; ANGPT2; REEP1; FLT1; FER1L3; SLC6A16; Normal DNMT1 <0.001 0 - down 500 40 AGMAT; PBX2; MPPED2 SHCBP1; MCM10; TUBB; NCAPH; TOP2A; TPX2; SPAG5; ANP32E; KIF20A; CCNB2; CDC45L; BUB1; KIF11; PLK4; TIMELESS; MAD2L1; KIF2C; H2AFZ; Relapse DNMT1 <0.001 0 - down 400 23 CKS1B; ZWINT; RAD51; NPR3; FLJ13197 C11orf49; NSUN5; SLC25A12; PIGB; EFHA1; HDAC1; GCLC; TMCO1; MTX2; NSUN5B; EXTL2; NSUN5C; YLPM1; AKAP2; BID; ARF4; NGLY1; C13orf23; MRPL16; ATIC; DLEU2L; LOC137886; PTBP2; TFG; PMS2L8; PALM2-AKAP2; XYLT1; MSL2L1; AGL; RHOBTB1; AUH; ARID4B; KIAA0182; DNAJB6; SR140; SLC25A46; PCM1; SFRS12; MDM1; SLC46A3; PMS2L1; RBBP4; SLC4A7; CD47; Hyperdip>5 ADNP; RHOBTB3; C1orf181; PTCD3; CYFIP2; SHMT2; LZTFL1; FAM60A; GCC2; 0 DNMT3B <0.001 0 - down 1000 227 VPS13A; TMED5; IQCB1; SSX2IP; TGDS; KARS; FBXL14; PTP4A2; DYNC2LI1;

Suppl. Table 3 – page 31

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

ZC3H7A; Gcom1; C2orf25; TFRC; PWP1; DSTN; IPW; ATR; RRP15; ANKHD1; SCP2; NSUN6; FUBP1; TMEM38B; ZNF195; PATZ1; TWF1; ANAPC5; TFB2M; CEP110; PRPF38B; EPRS; UBA3; NME7; CTSC; MTIF2; ELOVL5; SLC25A13; SNX4; MTMR2; SNRPE; CBFB; ZBTB11; INSIG1; ITM2A; SH2B3; HIST1H2AI; BANK1; CCDC109B; GABBR1; MGP; DSE; LILRB2; CD9; LDOC1; STX7; CCND2; SLC16A2; TSC22D3; C14orf113; BACE1; NOS2A; NPR1; TREML2; HLA- B; SPRY4; SCN1B; LARGE; CENTD1; RHBDF2; HIST1H1C; RIN2; IFI30; MID1IP1; TFEB; HLA-DMB; DNASE1L1; CBR3; FHL1; CDKN1A; HLA-G; ECM2; XAF1; HLA-J; SLC35E3; HCP5; NAV1; HLA-F; TGIF1; KANK2; ARSD; XBP1; NEO1; VIPR1; OAS1; EPHA7; FUT7; IRF7; ELK3; NPY; SLC43A3; NDST1; KLF11; NCF2; ZNF467; PRSS7; TBC1D9; IGFBP4; TMEM50B; PDLIM1; IFI35; TRPM2; TNFSF13; RGL1; FGD1; WDFY3; FAM26B; CD86; IKBKG; ERG; PPM1F; PPAP2B; IRF9; KIAA0774; FAM49A; KBTBD11; IFIT3; C17orf60; MRC1; UNC93B1; PDE4B; TNNI2; GNA11; CDC42BPB; PLVAP; LGMN; IRF8; TLR1; C10orf10; IFIT1; CIDEB; SIGLEC15; ENOX2; RBM47; TLR2; ALOX5; CELSR1; DLG3; SH3BP2; CYBB; CYTL1; ECHDC3; NDE1; CBR1; ARHGEF10; PIP3-E; IL6R; EFNB1; IFNGR2; PDXK; MX1; SETBP1; LOC57228; ALDH3B1; LTB4R; CEBPE; SH3BP5; HDHD1A; ITSN1; MYBPC2; ACOT9; SCML2; ADAM8; IL13RA1; IL3RA IQGAP2; KIAA0564; FAM120A; ATP8A1; NIT2; DECR1; PTPN2; MPZL1; CABC1; SYNJ2; AMD1; SLC39A8; BRP44L; PXMP3; MRPL3; CTSC; ALDH9A1; JARID2; CASP4; PPIF; NEUROD1; LETM1; MTX2; SRPRB; SRP72; UCHL5; WAPAL; CD96; KLHL21; C15orf15; TPP2; MINPP1; MRE11A; EIF3M; HEATR3; TFB2M; WDR43; TRIB2; ITGA4; HADH; XYLT1; DHRS7; SMAP1; RFK; PTER; KTELC1; OSBPL3; ATIC; BRP44; STX6; VPS54; ASAH1; SLC1A4; GALC; WWOX; LRPPRC; HINT1; C21orf91; AACS; LRRFIP2; SLC7A1; POGK; MRPL9; NUP98; RPIA; POLR3E; HSPA14; ATP2C1; PRMT3; C11orf57; HK2; LGTN; LDHB; CLNS1A; TMCO1; RRP15; BZW2; CPSF6; CAPRIN2; MRPS30; GPSM2; AGL; FAM8A1; UBA5; ADA; TRMT11; PCM1; PLXNC1; CEPT1; PIK3CB; SHQ1; KIAA0182; H6PD; SNRPE; FAH; C2CD2; ITGAE; KIAA0125; NSUN5; USP20; THOC7; KIAA0776; IKBKAP; EPRS; C12orf11; LARP1; AMPD2; LANCL1; IDH1; WDR67; GCSH; TEX261; ANKRD27; PIGB; CDC2L6; ATP13A3; DLG3; SPP1; MYO1B; SCARF1; CD74; WSB2; KIAA0427; CSDA; CD97; SNX2; POU4F1; PRSS7; C11orf75; TAZ; LAPTM5; FAIM3; CDS2; CCND2; SOCS2; TCF4; HIST1H2AE; PQLC1; AGPAT2; PPP1R16B; EFNA4; NRXN3; HLA-DOA; IGKV1OR2-108; DOK3; IL24; HLA-DQB1; MAN1A1; HLA-DRA; MAP4K2; HIST1H2BK; EPHB4; SH3TC1; TP53TG3; RNF141; SMTN; BCL3; IGHA1; VCL; CEBPE; LARGE; PTPN12; HLA-DPB1; MAMLD1; HLA-DPA1; AKAP12; MDM2; SCML2; HLA-DRB1; APBB1IP; HSPB1; DUSP26; FAM127B; HIST1H2AJ; NPY; TEL-AML1 DNMT3B <0.001 0 - down 1500 334 SERPINB9; HIST2H2AA3; CD52; GIMAP4; HIST1H3H; PFTK1; IFI16; HIST1H2BI;

Suppl. Table 3 – page 32

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

TMEM140; HLA-DRB5; CTGF; PLXNA3; HIST2H2BE; C9orf91; PTPRE; HIST1H2BE; WFS1; DGCR6; KIAA1539; TCL1B; CHD7; CTNNA1; TGFB1I1; MYLK; CLCN7; HIST1H2BG; HRK; HLA-DRB6; HIST1H2BH; SSX4; CCR1; MEF2C; CD40; KANK2; CEACAM1; EFEMP2; HLA-DMA; HLA-DMB; C1orf78; HIST1H2BD; AP1B1; EFNA1; CRIM1; PTPRG; CSF3R; tcag7.1314; MME; VPREB3; UTRN; LAIR1; SSX2; ST3GAL6; FADS3; ZNF274; MGC5370; RGL1; TSPAN14; LST1; PYHIN1; NPR1; MYO5C; DIP2C; FAM127A; ERG; HIST1H2BF; NEIL1; CD79A; C1orf38; HMGB3; SIGLEC15; JUP; FBXW7; CACNA1A; FGD1; JMJD2B; LILRA2; HS3ST1; PLCL2; MLXIP; LDOC1; VAMP5; GAB1; COL5A1; PXN; SLC27A3; DPEP1; FHIT; FAM50A; POU2AF1; FOXO1; GTF2IRD1; INSR; SLC35E3; PTK2; FAM65A; BTN2A2; TRIB1; LTB; SCHIP1; ITPR3; EGFL7; INTS3; C14orf132; ALOX5; NOL4; PRO2268; FCGRT; AK1; EPHA7; ISG20; BMP2; GNG7; ELK3; CKMT2; PSD3; LASS4; TBC1D8B; ITPR1; STK32B; GPR17; DUOX1; EDEM1; GABBR1; CD27; SDC1; KHDRBS3; NARFL; FERMT2; GRK5; SEMA6A; HLA-DOB; TBC1D9; H1F0; STAG3; SPTA1; CYB5R2; WDFY3; PID1; MAPK13; MDK; PTP4A3; RAG1; FUCA1; NRN1; TRPM4; SEMA3F; PDLIM7; TERF2; DRAM; PTPRK; NR3C2; SPANXA1; KCNK3; GBA3; ARHGAP29; TMEM16A; FBN2; TNS1; PCLO EFTUD1; ANP32A; EFHA1; HDAC1; TMCO1; EIF3K; MAP2K2; YLPM1; PSME4; BID; NUP93; NDUFA7; ARF4; PSMA5; MRPL16; ATIC; UQCRH; IDH3B; RTCD1; FLJ14154; ZNF131; TFG; MRPL48; WDR61; MSL2L1; NHP2L1; HSPC152; DNAJB6; SR140; SLC25A46; PCM1; CIAPIN1; SFRS12; MDM1; RBBP4; CD47; C1orf181; COX7A2L; PTCD3; SNRP70; EXOC3; NGRN; ATP5L; FIBP; TAF9; TMED5; SNRPA; KARS; FBXL14; PTP4A2; ZC3H7A; CYCS; LONP1; C2orf25; PWP1; C19orf53; ATR; ADSL; ADAM10; IHPK2; PPM1G; UGP2; ANKHD1; SFI1; SCP2; ATF4; ETF1; TWF1; ANAPC5; NDUFA13; PRPF38B; C1orf77; NDUFB3; ATP5B; UBA3; DLG1; COX5A; HSBP1; SNX4; LOC440354; MTCH2; NDUFA3; PIN1; YARS; NDUFS8; CBFB; MLH1; ZBTB11; ARPP-19; ZDHHC4; GABARAPL2; INSIG1; GABBR1; MGP; CD9; LDOC1; KIAA0427; CCND2; IER3; C14orf113; BACE1; NOS2A; NPR1; TREML2; IFIH1; HLA-B; SPRY4; SCN1B; LARGE; HIST1H1C; NEDD9; RIN2; OAS2; HLA-DMB; HERC5; HLA-G; OR2A9P; ECM2; CYB561; XAF1; HLA-J; HERC6; SLC35E3; POU4F1; HCP5; NAV1; HLA-F; KANK2; ARSD; NEO1; VIPR1; SERPING1; OAS1; EPHA7; ZNF516; FUT7; IRF7; ELK3; NPY; NDST1; ZNF467; SERPINB6; PRSS7; F2RL1; PDK3; TBC1D9; PDLIM1; IFI35; RGL1; FGD1; WDFY3; CD86; CLEC4E; ERG; TMEM165; EXDL2; IL1B; PPAP2B; GSTA4; IRF9; PTPRE; KIAA0774; IFIT5; IFIT3; IFI44L; C17orf60; MRC1; H2AFY2; PDE4B; NGFR; TNNI2; GNA11; CDC42BPB; LGMN; TLR1; C10orf10; IFIT1; CIDEB; SIGLEC15; OGFRL1; RBM47; TLR2; DDEF1; CSF3R; Hyperdip>5 ALOX5; CELSR1; DLG3; CYBB; CYTL1; ECHDC3; PIP3-E; IL6R; EFNB1; MX1; 0 HDAC1 <0.001 0 - down 1000 207 SETBP1; LOC57228; LTB4R; CEBPE; SH3BP5; ITSN1; MYBPC2; SCML2;

Suppl. Table 3 – page 33

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

MS4A6A; C10orf56; IL13RA1; IL3RA; ZNF185 PSMA7; MRPL34; COX6C; BID; UCRC; TIMM8B; ENSA; MAPBPIP; NDUFA6; NDUFS6; RAN; COX6A1; MRP63; PSMD2; FKSG30; MRPL13; MDH1; NDUFS1; CD34; TP53TG3; CCR5; MYLIP; APOL6; GRIK2; RASL10A; PDE8B; TOX3; EGFL7; GNG11; FLRT3; CHD7; EFR3B; PRKG2; ABCB4; ZNF239; ZNF192; CSHL1; RXRA; CDH11; ANGPT2; ITGA6; REEP1; FLT1; PCBP4; FER1L3; AGMAT; LGR5; PBX2; TXNRD3; MPPED2; HEY2; LHFPL2; CHST7; GFOD1; Normal HDAC1 <0.001 0 - down 1000 56 PTPRM; CENTG2 PRDX3; NDUFA1; TRMT5; COPS3; COX7B; FRG1; LAGE3; HMGN2; SMS; RBBP7; PSMC5; UBE2A; TBC1D25; ATP5J; HMGN1; SOD1; HMGN3; PECI; NDUFB8; CCDC56; EIF4A3; H2AFZ; C4orf27; RWDD1; SF3B5; PGAM1; MRPL13; PSMA3; NDUFA8; TP53TG3; CCR5; APOL6; GRIK2; CBLB; RASL10A; FLRT3; Normal HDAC2 <0.001 0 - down 500 44 EFR3B; PRKG2; ZNF192; CSHL1; REEP1; PCDH9; FER1L3; AGMAT C4orf41; SIRT1; NUP54; RAB5A; PSMC6; COPS4; TCEAL1; HNRPH2; NDUFB8; PIN4; BZRAP1; GRIK5; SSH3; GLT25D1; HRK; ERBB2; GPR176; SH2B2; PCDH9; Pseudodip HDAC2 <0.001 0 - down 1500 27 dJ222E13.2; HCRP1; SERHL2; TAP2; ATM; SLIT2; PALM; SFRS6 C11orf49; EFTUD1; NSUN5; BTG3; HDAC1; ODC1; TMCO1; MTX2; PKIA; EXTL2; C9orf16; FLJ11506; AKAP2; TMEM183A; C13orf23; MRPL16; ATIC; C16orf24; LOC137886; PTBP2; MINPP1; FLJ14154; ITPKB; TFG; MRPL48; PALM2-AKAP2; MSL2L1; AGL; RHOBTB1; PIK3R3; KIAA0182; DNAJB6; SLC25A46; GTPBP8; SLC4A7; NFATC1; CSRP1; CYFIP2; IFI35; ACSL5; TRPM2; RGL1; FGD1; TNFRSF10B; ERG; PPM1F; PTPRE; FAM49A; IFIT3; C17orf60; Hyperdip>5 MRC1; PDE4B; TNNI2; GNA11; LGMN; IRF8; TLR1; CIDEB; DDEF1; ALOX5; 0 HDAC4 <0.001 0 - down 500 68 CYBB; CYTL1; ECHDC3; EFNB1; LOC57228; LTB4R; SCML2; IL3RA CAPG; NUCKS1; NDUFS5; PSMA7; APIP; MRPL34; PITPNC1; COX6C; TOR3A; MAGEF1; NUBP2; RNPEP; NANS; SS18L2; PSMB3; SCCPDH; BID; SEC24D; ARL3; UCRC; SYNJ2; TIMM8B; ARPC5; PTTG1; FH; MAPBPIP; CCNB2; TUBA1C; RPA3; HN1; NDUFB8; CBX1; ATP5G1; H2AFZ; NDUFA6; NDUFS6; GPI; COX6A1; SFRS2B; INTS7; MRP63; PSMD2; SF3B5; TUBB2C; PGAM1; FKSG30; MRPL13; GRAMD4; NCAPD3; MDH1; NDUFS1; CD34; TP53TG3; CCR5; MYLIP; APOL6; MXI1; DLGAP4; RASL10A; PDE8B; EGFL7; AKAP12; GNG11; CHD7; MEF2A; ABCB4; ZNF187; PTGDR; APOBEC3G; RXRA; TLE4; ITGA6; FLT1; CASK; PCBP4; AP1B1; FER1L3; CAPN3; LGR5; PBX2; HEY2; Normal HDAC4 <0.001 0 - down 1500 86 LHFPL2; GFOD1; STAP1; PTPRM; CENTG2 PRPS2; SMYD2; PTGER4; UCK2; CCDC86; LPXN; DPH4; NUP210; DECR1; PTPN2; CABC1; ZNF593; ACOT7; SYNJ2; CDKN2D; BRP44L; PXMP3; MRPL3; CTSC; ALDH9A1; CIB1; JARID2; PTPN6; ACAT2; NFATC1; PPIF; FDX1; C9orf16; LETM1; MTX2; C8orf33; GRAMD4; UCHL5; WAPAL; MRLC2; CD96; TPP2; CSRP1; MINPP1; SRI; TFB2M; TRIB2; SF3B5; MRPS34; RFK; RAP2B; LSM4; TEL-AML1 HDAC4 <0.001 0.08862 - down 1000 237 ATIC; BRP44; STRAP; ADARB1; ADAM10; ARL3; CDK2AP2; SLC1A4; AACS; Suppl. Table 3 – page 34

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

POGK; MRPL9; APEH; KATNA1; RPIA; HSPA14; SPON2; RABIF; LDHB; CLNS1A; TMCO1; CPSF6; CAPRIN2; FH; HLA-DOA; IGKV1OR2-108; DOK3; HLA-DQB1; MAN1A1; HLA-DRA; HIST1H2BK; EPHB4; SH3TC1; TP53TG3; TNFRSF10B; AHDC1; RFTN1; LARGE; PTPN12; SLC12A6; C1orf165; HLA-DPB1; MAMLD1; HLA-DPA1; SCMH1; MDM2; SCML2; HLA-DRB1; DUSP26; HIST1H2AJ; NPY; SERPINB9; HIST2H2AA3; RDX; CD52; GIMAP4; PFTK1; IFI16; HIST1H2BI; TMEM140; HLA-DRB5; CTGF; HIST2H2BE; PTPRE; HIST1H2BE; WFS1; DGCR6; KIAA1539; TXNIP; CHD7; MYLK; APP; CLCN7; HIST1H2BG; HRK; HLA-DRB6; HIST1H2BH; SSX4; CCR1; MEF2C; TMEM2; CD40; LYL1; KANK2; EFEMP2; HLA-DMA; HLA-DMB; ZCCHC14; AP1B1; EFNA1; CRIM1; PTPRG; CSF3R; ZMIZ1; tcag7.1314; MME; VPREB3; HHEX; CLCC1; UBA7; UTRN; LAIR1; SSX2; ST3GAL6; PLCXD1; ZNF274; MGC5370; RGL1; TSPAN14; CD200; LST1; NPR1; MYO5C; ERG; HIST1H2BF; REL; CD79A; C1orf38; ZNF117; ENTPD4; SIGLEC15; MAPK8IP3; IL6ST; JUP; FBXW7; FGD1; LILRA2; HS3ST1; OCA2; MLXIP; LDOC1; GAB1; COL5A1; SLC27A3; DPEP1; FHIT; POU2AF1; FOXO1; INSR; SLC35E3; PTK2; FAM65A; BTN2A2; TRIB1; SCHIP1; ARHGAP24; EGFL7; INTS3; DNMBP; ALOX5; NOL4; PRO2268; AK1; EPHA7; ISG20; BMP2; GNG7; ELK3; CKMT2; PSD3; TBC1D8B; ITPR1; STK32B; DSC2; EDEM1; GABBR1; MSR1; SMAD1; WASF2; SEMA6A; SCARB1; HLA- DOB; TBC1D9; STAG3; GNG11; SPTA1; CYB5R2; WDFY3; MDK; C13orf18; PTP4A3; RAG1; FUCA1; SEMA3F; TERF2; DRAM; NR3C2; KCNK3; HAP1; TNS1; PCLO FRAT2; GLUL; DGKD; WASF1; RABL4; RCOR1; ORC5L; GCNT1; CLASP2; ZEB2; RB1; C1GALT1; KTELC1; BLK; ODC1; SLC4A7; HK2; APBB2; PPFIA1; PTPN2; P2RX5; FLI1; SNX4; LOC57228; CLSTN1; FHIT; PRKCH; SQRDL; PLXND1; KHDRBS3; TCF7L2; EMP2; P2RY5; CTDSP2; MDM2; GIPC1; TMEM134; DDR1; PDXK; MGC29506; NEDD4; PTPLA; BRF1; RASL10A; HIF1A; CCDC88C; ETV6; MME; NEDD9; CRIP2; HDAC7; HLA-DPB1; SH3BP5; ITPR1; EMILIN1; OPTN; PRKCA; BBC3; TXNIP; C13orf15; LGMN; ST3GAL5; LAIR2; HLA-DQB1; EDEM1; LST1; YES1; EGLN1; HBS1L; HSPB1; PVRIG; C11orf75; PXN; IFITM1; MYLK; LARGE; CD52; MED9; ILVBL; SERHL2; PECAM1; A2M; IFITM2; VAMP5; MAP3K11; SYNE2; PTPRD; EFNA1; FXYD6; ID3; RPL23AP13; GPR56; ZNF467; DNTT; TncRNA; HLA-DQA1; XBP1; GAB1; DUSP26; RAB13; CD34; CTNNBIP1; AMBRA1; SERPINB9; RAI14; MRC1; STARD3; LAIR1; MYO5C; PTPN18; RAB11A; NAV1; TNFRSF14; SV2A; SCHIP1; FBXW7; FYN; FZD6; MYO1B; BST1; IFITM3; FARP1; PDE9A; PHF15; ITGA6; CD99; CENTD1; C6orf32; CD27; NRXN3; BMPR1B; GIMAP4; PALM; FLJ20489; ITGA5; CCND2; OSBPL10; GIMAP6; FSCN1; RAPGEF3; COLQ; ARHGEF17; MGC4655; GADD45A; GIMAP5; SEMA6A; ASB13; FAM129A; PRX; TUBA4A; COL6A3; BCR-ABL HDAC9 0.009 0 - down 1500 160 NPDC1; CDS2; CASP10; CNN3; ECM1; SLC2A5; LOC26010; OLFML2A; CTDSPL

Suppl. Table 3 – page 35

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

MSN; ARHGAP4; OGT; WDR44; TMED10; MORC3; EXOC1; CSNK1D; TMEM30A; KIAA1109; ZFP106; FAM134C; TUBGCP2; CLINT1; ATP6AP2; UBE2D3; TMEM164; LAMP2; PAFAH1B1; RPS6KA3; RP6-213H19.1; SSR4; WSB1; SERINC1; TM9SF1; ARAF; WDR42A; RUVBL1; ZDHHC7; GCN5L2; MCM3AP; IL10RB; GDI1; KIAA0831; GLOD4; WDR45; ASMTL; UBR2; VTI1B; PGK1; SFRS17A; MECP2; BTAF1; RGS5; CDC14B; SEMA6D; MUC5AC; FADS3; ENTPD3; HIST1H4C; SPPL2B; AKAP12; CPM; FLJ13769; MLPH; C6orf124; MYLK; KCNJ2; CD84; FERMT1; CD48; PIP5K1B; SEMA5A; MDM4; PCSK5; PLS3; ATRNL1; GLDC; TRAK2; GPATCH2; TRIM16; C1orf135; RAG2; ST6GALNAC4; ZNF124; ARHGEF11; CSRP1; TCF3; MYL4; JAM2; PAWR; GATM; PPFIBP1; KCNJ16; BIK; EPB41L2; VDR; EMP2; CORO2B; ARNTL2; MAP3K1; EWSR1; LTBP2; CASC1; MAP1B; GPR176; ODZ4; QRSL1; TSSC1; FNDC3B; ALDH1A1; SYT1; CALD1; RASAL1; ELOVL2; IL12RB2; APBB2; KCNMB3; IRF4; AOX1; ROR1; DACT1; KCNJ12; FAT; SORBS1; SEMA4C; E2A-PBX1 HDAC6 <0.001 0 - down 750 125 SLAMF1; GP5; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; PBX1 HPRT1; SLC10A3; NDUFA1; HSDL2; COX7B; LAGE3; SMS; RBBP7; UCHL5IP; PSMC5; UBE2A; TBC1D25; ETHE1; ATP5J; PGD; HMGN1; ARMCX1; FLII; SOD1; BCAP31; C21orf59; RCOR1; HMGN3; AHSA1; SLC25A5; LRPAP1; EIF4A3; EBP; SLC9A6; PHB; AMPD3; HSPA5; MCTP2; GPHN; TP53TG3; APOL6; GRIK2; CBLB; RASL10A; TOX3; KAL1; AKAP12; FLRT3; EFR3B; PRKG2; ZNF239; PTGDR; CD84; ZNF192; CSHL1; ANGPT2; REEP1; GRAMD1B; FLT1; RAG2; LRRC8B; PCDH9; GLDC; FER1L3; AGMAT; PHYH; TXNRD3; MPPED2; HEY2; Normal HDAC6 <0.001 0 - down 1500 68 LHFPL2; STAP1; PTPRM; CENTG2 SPIN2B; GSPT2; PIGA; ALG13; BACH1; RP2; C4orf41; SIRT1; RRAGA; NUP54; TMEM164; PSMC6; COPS4; LAMP2; TCEAL1; HNRPH2; PIN4; BZRAP1; GRIK5; Pseudodip HDAC6 <0.001 0.06117 - up 1000 27 ANXA4; ERBB2; GPR176; PCDH9; dJ222E13.2; SERHL2; SLIT2; SFRS6 HPRT1; LMAN2; TRMT5; NDUFB2; COPS3; COX6C; LAGE3; HMGN2; PSMC5; PSMB3; ATPIF1; TBC1D25; ATP5J; PGD; HMGN1; COPS6; UCRC; FLII; BCAP31; ENSA; RCOR1; HMGN3; AHSA1; PECI; NDUFB8; CCDC56; EIF4A3; NDUFS6; GPI; ARL6IP1; RAN; COX6A1; SFRS2B; MRP63; RWDD1; PSMD2; SF3B5; PGAM1; U2AF1; PSMD4; IQGAP1; MDH1; NDUFS1; PSMA3; HSPA5; NDUFA8; MCTP2; CD34; GPHN; RIMS3; TP53TG3; CCR5; APOL6; GRIK2; MXI1; CBLB; DLGAP4; RASL10A; PDE8B; TOX3; EGFL7; KAL1; HIP1; AKAP12; FLRT3; EFR3B; PRKG2; ABCB4; ZNF239; PTGDR; CD84; ZNF192; CSHL1; RXRA; CDH11; ANGPT2; LIG4; REEP1; RP1-21O18.1; FLT1; RAG2; LRRC8B; PCDH9; PCBP4; GLDC; RHBDL2; FER1L3; SLC6A16; CAPN3; AGMAT; LGR5; PBX2; Normal HDAC3 0.006 0 - down 2500 100 TXNRD3; MPPED2; HEY2; LHFPL2; CHST7; STAP1; PTPRM; CENTG2 MGC29506; CD2AP; ATP2B4; PRKCH; TNFRSF14; C11orf75; GIMAP4; FAM134B; YES1; RHOF; RYK; NDFIP1; PBXIP1; EDEM1; FAM117A; ZNF512B; TSPAN7; MLL HDAC7 <0.001 0 - down 750 104 GPR56; SLC5A3; ABLIM1; CEP68; LTB; GIMAP6; CCDC92; POGZ; PPP1R16B;

Suppl. Table 3 – page 36

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

FGFR1; PLCG1; C6orf32; GIMAP5; LST1; BTN3A3; CANT1; BEX4; STAT5B; NF1; ENOSF1; ITPR1; ICAM3; PVRIG; SERINC5; HDAC7; SPTAN1; MKL2; KIAA0317; SETD5; FAM102A; FYN; FUT8; ZMAT3; SERPINB8; WIT1; SPIB; NIP7; SMURF1; HDAC9; SERPINI2; NR5A2; PCDHGA11; RHOQ; EHD4; XYLT1; DGKD; B3GALNT1; MPEG1; UCK2; TBCC; RGS16; FOSL2; FXN; MARCH3; PUS7; SPG20; STARD13; CLEC2D; VNN1; VLDLR; ADK; PTGES3; BCAS4; STS; PRKCE; ZEB2; IGFBP7; PTCH1; THSD7A; CEBPA; CD72; C11orf24; CD44; GREM1; ADCY9; TUBB6; ACSL1; GPM6B; SCPEP1; RHOBTB3; MPZL1; MAP7; ABHD4; ATP8B4; MAP3K5; CCNA1; C20orf103 TAF10; RNF40; EFTUD1; ANP32A; TOMM22; SLC25A3; ITPA; EFHA1; HDAC1; THADA; FUS; MCRS1; PGLS; PAIP1; C1orf160; C9orf16; RER1; EIF3K; TH1L; GDE1; MAP2K2; YLPM1; PSME4; RMND5A; PRKCSH; BID; NUP93; TMEM183A; NDUFA7; ARF4; NGLY1; SF3A1; C13orf23; PSMA5; UPF1; IQCC; MRPL16; ATIC; TXN2; PSCD2; WDR77; MRPS27; UQCRH; HEATR1; IDH3B; RTCD1; ZNF131; MAT2A; TFG; MRPL48; EIF4ENIF1; WDR61; PMS2L8; MSL2L1; NHP2L1; C20orf30; HSPC152; BRD9; MASP1; SR140; NCBP2; AP3B1; SLC25A46; PCM1; CIAPIN1; SFRS12; PMS2L3; MDM1; ARPC1A; OGFOD1; PMS2L1; RBBP4; CD47; ADNP; MCAM; C1orf181; UCHL3; COX7A2L; PTCD3; STUB1; SHMT2; ACP1; FAM60A; CLEC16A; ATP5G2; NGRN; FIBP; TAF9; C12orf10; EIF3D; SNRPA; ARID1A; PSMF1; KARS; NOL12; FBXL14; PTP4A2; ARIH2; RFWD3; ZC3H7A; GNB1; Gcom1; CYCS; SNRPF; EIF3EIP; LONP1; C2orf25; MYO9B; PWP1; DCTN1; GTF2F1; C19orf53; ATR; ADSL; CALU; INPP4A; CSNK2A1; TEX10; IHPK2; PPM1G; ANKHD1; HNRPUL1; HTATIP; SCP2; ATF4; FUBP1; ETF1; RABL2A; ZNF195; C12orf47; PATZ1; FAM89B; ANAPC5; NDUFA13; TRIM28; CYC1; EPRS; C1orf77; ATP5B; PNKP; UBA3; DLG1; COX5A; PPP6C; ERGIC3; PAFAH1B3; SUPT5H; DDX41; HSBP1; SNX4; CAPRIN1; MTCH2; RPL24; EIF3J; NDUFA3; DNAJA3; PIN1; USP21; YARS; OBFC2B; SNRPE; NDUFS8; PHKG2; CBFB; MLH1; MPV17; HNRNPU; ZBTB11; ZDHHC4; GABARAPL2; PCBP2; ASXL1; DRAP1; SMPD4; BZW1L1; RNASEH1; PRPF19; TERF2IP; VPS13B; HNRPK; SMARCC1; EIF3I; SKP2; EIF4G1; ACADM; EXOSC2; SFRS9; APEH; SERBP1; TUFM; ATP6V1B2; ATP5SL; UBAP2L; DDX39; POLR3E; YEATS2; HIATL1; HMOX2; CHD4; GRSF1; PSMC3; ATP1B3; PRCC; RBM8A; CSDE1; C5orf13; GTF3C3; GPR89B; HYOU1; LEPROTL1; GTF3C2; CIAO1; SSSCA1; PTDSS1; ZNHIT1; HARS; WDR70; ATP5D; ATP5G3; KHSRP; GTF2I; ATP6V0A2; NDUFA10; POLR2J; HNRNPA1; SF3B1; GSPT1; TIA1; RANBP1; MAP4; MRPL3; FXR1; DHPS; CCT5; FIS1; C20orf11; EIF3M; COPZ1; COX4NB; SLMO2; DCTN6; FAM120A; OAZ1; CHMP1A; EIF2B5; COX4I1; AP3D1; SEP15; C3orf60; RBM39; ST13; CPSF6; BCL7B; ACO2; HMGB1; USP7; Hyperdip>5 TUBB3; C20orf24; ASCC2; EIF2B1; THOC5; SKIV2L2; YKT6; UFC1; FBL; 0 SMARCC1 <0.001 0 - down 2000 529 NCBP1; ACTL6A; TFPT; MAMLD1; PHF1; SERPINB9; WFS1; NR4A2; SLC6A16;

Suppl. Table 3 – page 37

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

IFI27; SIRPA; VNN1; OPTN; HIST1H2BH; C14orf139; STK32B; MYO1B; 3.8-1; BTK; HIST1H2AJ; NUAK2; TSPAN13; CEACAM6; RAI14; HIST1H2BI; IGKV1OR2-108; HERC3; LAT2; ST3GAL6; P4HA2; GALNAC4S-6ST; TRIM38; ADM; CNN2; PRO2268; EFNA1; HIST1H2AM; NR4A1; LHFP; HLA-DRB5; SCNN1A; KLF9; DGCR6; C1orf38; HLA-DPA1; TCL1A; CLOCK; TCF4; HLA- DRB1; LMO2; SLC27A3; CTBP2; CD69; CAST; HIST1H2BK; LXN; LILRB3; KIF13A; LILRB1; BLNK; EMP1; VPREB1; TLR7; EIF2AK2; MGC5370; FXYD6; HLA-DRB6; SCHIP1; P2RY14; EPHB3; MAP3K8; CCR6; GPR171; HLA-DQB1; KLHL2; OFD1; LY86; CRAT; CENTA2; PTK2; PRKAG2; ECM1; ENTPD1; C14orf132; HSPA1B; TBKBP1; TNFRSF1B; STAB1; S100A13; SCARF1; HIST1H2AI; BANK1; GABBR1; MGP; DSE; LILRB2; CD9; LDOC1; KIAA0427; STX7; HSPA2; CCND2; IER3; SLC16A2; ST7; SGSH; TSC22D3; C14orf113; BACE1; NOS2A; ULK2; NPR1; TREML2; HLA-B; SPRY4; SCN1B; LARGE; RHBDF2; HIST1H1C; NEDD9; ZRANB1; RIN2; IFI30; KIAA0513; TFEB; KIF1B; HLA-DMB; BCL2L2; FHL1; OR2A9P; ECM2; GPR56; CYB561; XAF1; HLA-J; HERC6; SLC35E3; POU4F1; TIE1; RCAN1; HCP5; NAV1; HLA-F; DUSP3; KANK2; NEO1; VIPR1; OAS1; EPHA7; ZNF516; FUT7; IRF7; ELK3; NPY; NDST1; KLF11; NCF2; ZNF467; KIAA1462; SERPINB6; PRSS7; F2RL1; PDK3; TBC1D9; DYNLT3; IGFBP4; PDLIM1; HLA-A; IFI35; ACSL5; TRPM2; TNFSF13; RGL1; FGD1; WDFY3; STYK1; CD86; CLEC4E; CCL3; ERG; PPM1F; TMEM165; ERCC6L; EXDL2; LGALS3BP; IL1B; PPAP2B; FLT3; GSTA4; IRF9; PTPRE; MGAT4A; MAGT1; OCRL; KIAA0774; FAM49A; PECAM1; KBTBD11; IFIT3; IFI44L; C17orf60; MRC1; UNC93B1; H2AFY2; PDE4B; NGFR; SAT1; TNNI2; GNA11; RRAGB; CD1C; CDC42BPB; PLVAP; LGMN; IRF8; TLR1; C10orf10; IFIT1; CIDEB; SIGLEC15; ASB9; OGFRL1; ENOX2; RBM47; PLCH1; TLR2; CSF3R; ALOX5; CELSR1; SH3BP2; PRKAR2B; CYBB; CYTL1; ECHDC3; NDE1; CBR1; ARHGEF10; ZFYVE26; PIP3-E; IL6R; EFNB1; IFNGR2; PDXK; MX1; SETBP1; LOC57228; ALDH3B1; LTB4R; CEBPE; SH3BP5; HDHD1A; ITSN1; MYBPC2; ACOT9; GPRASP1; SCML2; MS4A6A; ADAM8; SCML1; C10orf56; IL13RA1; MORC4; IL3RA; ZNF185 ARPC1B; TRSPAP1; LMAN2; MRPL34; COPS3; ARPC3; C16orf33; PSMC5; MAGOH; PSMB3; DCI; FLII; PTTG1; FH; MAPBPIP; AHSA1; CTNNAL1; RFC4; PDIA6; EIF4A3; CBX5; TWF2; ARL6IP1; RAN; CLTB; GTF2E2; COX6A1; SFRS2B; PSMD2; TUBB2C; U2AF1; PSMD4; NDUFS1; HSPC157; CD34; GATA3; GPHN; TP53TG3; CCR5; APOL6; GRIK2; TOX3; KAL1; FLRT3; EFR3B; PRKG2; ZNF239; CD84; ZNF192; CSHL1; RXRA; ITGA6; REEP1; RP1-21O18.1; FLT1; CASK; PRUNE2; RGS9; FER1L3; SLC6A16; AGMAT; PHYH; TXNRD3; MPPED2; Normal SMARCD2 <0.001 0 - down 1500 69 LHFPL2; CHST7; GFOD1; CHST2; PTPRM LEPROT; MLC1; ARL6IP5; GSTK1; WIPI1; MAP3K5; ADCY9; MFSD1; HK2; CCR SMARCA2 <0.001 0.08084 - down 500 19 COMT; FEZ2; CDC25B; NUDT11; TCEA2; EIF4EBP2; MAGED1; SALL2; ZNF253;

Suppl. Table 3 – page 38

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

DBN1 TAF10; C11orf2; RNF40; C11orf49; EFTUD1; BTG3; ANP32A; SLC25A3; ITPA; EFHA1; HDAC1; LOC51035; MCRS1; TMCO1; PAIP1; C1orf160; EXTL2; C9orf16; EIF3K; FLJ11506; TH1L; MAP2K2; YLPM1; PSME4; RMND5A; HDGF; NUP93; TMEM183A; TTC15; NDUFA7; PCGF1; ADAM17; ARF4; NGLY1; PSMA5; MRPS34; PPME1; MRPL16; ATIC; USP4; PSCD2; WDR77; MRPS27; UQCRH; PTBP2; IDH3B; RTCD1; FLJ14154; ZNF131; TFG; MRPL48; WDR61; CTPS; MSL2L1; NHP2L1; REPIN1; HSPC152; BRD9; MASP1; SR140; NCBP2; AP3B1; SLC25A46; UCKL1; PCM1; CIAPIN1; SFRS12; MDM1; RBBP4; SF3A2; SLC4A7; CD47; C1orf181; COX7A2L; PTCD3; STUB1; SNRP70; EXOC3; FAM60A; CLEC16A; NGRN; PTPRA; FIBP; TAF9; TMED5; C12orf10; EIF3D; SNRPA; ARID1A; CHP; PSMF1; KARS; FBXL14; PTP4A2; ARIH2; C16orf57; ZC3H7A; CYCS; SNRPF; EIF3EIP; LONP1; C2orf25; PWP1; DCTN1; C19orf53; ATR; ADSL; EDC4; INPP4A; ZNF580; IHPK2; TMEM87A; ARFIP2; PPM1G; ANKHD1; SFI1; HTATIP; SCP2; ATF4; FUBP1; ETF1; PATZ1; TWF1; FAM89B; ANAPC5; NDUFA13; NUP133; TFB2M; TRIM28; EPRS; C1orf77; ATP5B; UBA3; DLG1; COX5A; PPP6C; MTIF2; DDX41; HSBP1; SNX4; LOC440354; MTCH2; EIF3J; NDUFA3; PIN1; YTHDC2; YARS; OBFC2B; SNRPE; NDUFS8; CBFB; SPTAN1; MLH1; ARPP-19; ZDHHC4; GABARAPL2; MARS; PMS1; GOLGB1; FADS1; SPSB3; DRAP1; SMPD4; WDR59; BZW1L1; PRPF19; ZFP64; TERF2IP; GNPAT; VPS13B; HNRPK; SMARCC1; EIF3I; SKP2; ACADM; SFRS9; APEH; TUFM; ATP5SL; UBAP2L; DDX39; POLR3E; TTC1; YEATS2; HIATL1; HMOX2; CHD4; GRSF1; NAT11; ATP1B3; PRCC; RBM8A; CSDE1; GTF3C3; GPR89B; HYOU1; LEPROTL1; GTF3C2; ABCD3; PTDSS1; SSBP3; ZNHIT1; HARS; DYNLL1; ATP5G3; KHSRP; GTF2I; NDUFA10; HNRNPA1; SF3B1; COPG; GSPT1; HAX1; RANBP1; UBA5; MAP4; MRPL3; FXR1; DHPS; CCT5; HRAS; C20orf11; EIF3M; COPZ1; PDE6D; SIAH2; COX4NB; SLMO2; DCTN6; FAM120A; POMP; HSPA4; MFN1; CHMP1A; EIF2B5; COX4I1; VRK3; AP3D1; VPS13C; SEP15; C5orf28; CDC16; FNBP4; NUCB2; NIPA2; RBM39; ST13; CPSF6; BCL7B; ACO2; USP7; HSPBAP1; TUBB3; C20orf24; ASCC2; EIF2B1; THOC5; YKT6; ZC3H13; UFC1; FBL; LYRM1; ACTL6A; TFPT; SMTN; MAMLD1; SERPINB9; WFS1; SLC6A16; IFI27; SIRPA; SLITRK5; MYO1F; VNN1; OPTN; HIST1H2BH; C14orf139; LRP3; STK32B; MYO1B; 3.8-1; BTK; HIST1H2AJ; CYB5R2; NUAK2; TSPAN13; CEACAM6; RAI14; HIST1H2BI; ZNF443; IGKV1OR2-108; HERC3; NUDT3; LAT2; ST3GAL6; P4HA2; HHEX; GALNAC4S-6ST; TRIM38; ADM; CNN2; PRO2268; EFNA1; HIST1H2AM; SYNGR1; DNTT; HLA-DRB5; SCNN1A; DGCR6; C14orf106; TNFSF10; LY6E; COL18A1; C1orf38; HLA-DPA1; MYLIP; TCL1A; CLOCK; TCF4; HLA-DRB1; TSPAN14; EPHB4; SLC27A3; RNF141; ALOX5AP; Hyperdip>5 HIST1H2BK; LILRB3; KIF13A; LILRB1; BLNK; EMP1; VPREB1; TLR7; MANBA; 0 SMARCD1 0.008 0 - down 2500 570 EIF2AK2; MGC5370; FXYD6; HLA-DRB6; ZNF165; SCHIP1; P2RY14; EPHB3;

Suppl. Table 3 – page 39

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

ABCD1; CCR6; GPR171; HLA-DQB1; KLHL2; LY86; CRAT; PTK2; PRKAG2; MED9; KIAA0368; ECM1; ENTPD1; C14orf132; GPX1; MBIP; HSPA1B; GPR132; USP18; HRSP12; TNFRSF1B; IFI44; STAB1; SPTLC2; FLJ43663; S100A13; IFI6; SCARF1; SH2B3; HIST1H2AI; BANK1; GABBR1; MGP; DSE; LILRB2; CD9; LDOC1; KIAA0427; STX7; TWSG1; HSPA2; CCND2; IER3; SLC16A2; ST7; SGSH; C14orf113; BACE1; MX2; NOS2A; DAPK1; ULK2; NPR1; TREML2; IFIH1; HLA- B; SPRY4; SCN1B; LARGE; RHBDF2; HIST1H1C; NEDD9; RIN2; IFI30; KIAA0513; PLEKHA1; OAS2; HLA-DMB; HERC5; CBR3; FHL1; CDKN1A; HLA- G; OR2A9P; ECM2; CYB561; XAF1; HLA-J; HERC6; SLC35E3; POU4F1; TIE1; HCP5; NAV1; HLA-F; DUSP3; TGIF1; KANK2; ARSD; XBP1; NEO1; BRWD1; VIPR1; SERPING1; OAS1; EPHA7; ZNF516; FLNB; FUT7; BCAR3; IRF7; ELK3; NPY; FRMD4B; NDST1; PLEK; NCF2; ZNF467; KIAA1462; SERPINB6; PRSS7; F2RL1; PDK3; TBC1D9; LSP1; DYNLT3; IGFBP4; TMEM50B; PDLIM1; HLA-A; IFI35; ACSL5; TRPM2; TNFSF13; RGL1; FGD1; WDFY3; STYK1; TNFRSF10B; NFE2; ETS2; CD86; CLEC4E; GALNT3; CCL3; IL17RA; ERG; PPM1F; DDX60; TMEM165; ERCC6L; EXDL2; LGALS3BP; IL1B; PPAP2B; TAF9B; FLT3; GSTA4; IRF9; PTPRE; MGAT4A; MAGT1; CDYL; OCRL; KIAA0774; IFIT5; FAM49A; PECAM1; KBTBD11; IFIT3; IFI44L; C17orf60; MRC1; PDE4B; NGFR; KCTD12; TNNI2; GNA11; CAMK1; RRAGB; CD1C; CDC42BPB; PLVAP; LGMN; HSPA1A; IRF8; TLR1; C10orf10; IFIT1; CIDEB; SIGLEC15; ASB9; OGFRL1; RPS6KA3; RBM47; PLCH1; GSPT2; TLR2; DDEF1; CSF3R; ALOX5; CELSR1; DLG3; SH3BP2; PRKAR2B; CYBB; CYTL1; ECHDC3; NDE1; CBR1; ARHGEF10; PIP3-E; LYST; IL6R; EFNB1; IFNGR2; PDXK; MX1; SETBP1; LOC57228; ALDH3B1; LTB4R; CEBPE; SH3BP5; HDHD1A; ITSN1; MYBPC2; ACOT9; SCML2; MS4A6A; PLP2; ADAM8; SCML1; C10orf56; IL13RA1; MORC4; IL3RA; ZNF185 NDUFA1; COPS3; COX6C; COX7B; FRG1; RBBP7; PSMC5; PSMB3; ATP5J; HMGN1; ENSA; SLC25A5; NDUFB8; ATP5G1; EIF4A3; NDUFS6; COX6A1; RWDD1; PSMD2; SF3B5; PGAM1; NDUFS1; PSMA3; MCTP2; TP53TG3; CCR5; APOL6; GRIK2; RASL10A; EGFL7; KAL1; FLRT3; EFR3B; PRKG2; ZNF239; Normal SMARCE1 <0.001 0.0326 - down 1000 42 ZNF192; CSHL1; REEP1; FLT1; FER1L3; AGMAT; TXNRD3 SLC39A8; C4orf41; SIRT1; RRAGA; NUP54; RAB5A; CD46; PSMC6; COPS4; ICK; ATXN3; ARHGDIB; HNRPH2; NDUFB8; PIN4; MRCL3; BZRAP1; GRIK5; SSH3; HRK; ANXA4; E2F2; ERBB2; GPR176; SH2B2; PCDH9; CXCR3; DLGAP4; dJ222E13.2; HCRP1; MPO; SERHL2; PYCR1; COL9A3; TAP2; ATM; SLIT2; Pseudodip SMARCE1 0.003 0.08862 - down 2500 39 PALM; SFRS6 NME2; C1QBP; CCDC28A; DECR1; PTPN2; AMD1; RP3-377H14.5; BRP44L; MBD2; MRCL3; ACAT2; CSGALNACT2; ME2; C8orf33; ATP5G1; SRP72; OLA1; C14orf108; MRLC2; PSMG2; SLC25A5; UTP18; EIF2S1; RPL23A; RSU1; MRPS35; RPL19; SF3B5; SMAP1; PSMD9; SF3A3; SRPK1; NDUFV2; BTF3; STRAP; STX6; TEL-AML1 SMARCE1 0.009 0 - down 1500 271 APEX1; MRPS18B; IDE; DDX47; TCP1; SNRPD1; MRPS10; MRPL9; FAM110A;

Suppl. Table 3 – page 40

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

GTF2H5; NUP98; RPIA; HSPA14; LDHB; NOL7; IGBP1; CCDC53; CPSF6; MRPS30; VPS4A; CUTA; ZNF22; EIF2B2; C14orf166; ATP5H; ARPC5; DHX40; SEH1L; CCT2; GTF2A2; CAMK2G; SNRPE; PFN1; ZNF32; C14orf156; THOC7; KIAA0776; NDRG3; HSP90AA1; PARK7; PSMA4; UXT; WRB; GIMAP5; UAP1L1; SUOX; SPP1; HEY2; DHRS3; TP63; CD74; EPB42; SP4; TMCC2; ATF5; MPL; ALAS2; SLC35F2; ERAF; DNM1; GYPB; PCDH9; SCARB2; SOCS2; ODZ4; AGPAT2; SELENBP1; MCTP2; OAS3; NRXN3; HLA-DOA; IGKV1OR2-108; DOK3; SLC4A1; HLA-DRA; TP53TG3; IGHA1; LARGE; SLC12A6; MORC1; HLA- DPB1; MAMLD1; AKAP12; MDM2; HLA-DRB1; APBB1IP; DUSP26; GYPA; CA2; GIMAP4; PFTK1; TSPAN5; TMEM140; HLA-DRB5; CTGF; UBE2H; WFS1; TCL6; TCL1B; COBL; TXNIP; MYLK; GTDC1; SSX1; CLCN7; HIST1H2BG; HRK; SSX4; CCR1; MEF2C; CD40; LYL1; CEACAM1; HPS4; EFEMP2; C1orf78; ATN1; PTPRG; VPREB3; UTRN; SSX2; FADS3; AMIGO2; MAGED4B; PYHIN1; NPR1; C12orf49; MYO5C; DIP2C; IL18RAP; CD79A; ZNF117; LRP8; LPHN3; FGD6; CACNA1A; FGD1; HS3ST1; OCA2; GAB1; FLRT3; COL5A1; CHL1; SLC27A3; PFKFB2; DPEP1; FHIT; POU2AF1; INSR; SIDT1; TRIB1; SCHIP1; IL1RAP; ARHGAP24; C15orf5; ITPR3; EGFL7; NOL4; PRO2268; CCNJL; EPHA7; CKMT2; TBC1D8B; STK32B; RICS; GPR17; LGALS7; DSC2; DUOX1; CACNB2; SPON1; CD27; MSR1; AJAP1; SDC1; KHDRBS3; NARFL; SMAD1; FARP1; FERMT2; GRK5; SEMA6A; EHD2; SDC2; TFPI; SCN3A; LONRF1; SH3GLB2; SCARB1; HLA-DOB; ANGPTL2; H1F0; STAG3; DLGAP2; GNG11; SPTA1; NRTN; PID1; MAPK13; ABCG2; MDK; EPOR; PLAG1; GREB1; C13orf18; PTP4A3; RAG1; NRN1; TRPM4; SEMA3F; CXCR7; TSPYL5; PDLIM7; TERF2; DRAM; PTPRK; MYO10; NR3C2; SPANXA1; KCNK3; TUSC3; GBA3; ARHGAP29; TNFRSF21; TMEM16A; LOC654342; NOVA1; HAP1; FBN2; TCFL5; TNS1; PCLO; BIRC7; CLIC5; ARHGEF4 CIRBP; MSN; LASP1; KIAA0430; TM9SF3; SNAP23; ITGB1; UQCR; ITM2B; AMZ2; OGT; TMED10; CNDP2; RNF13; UBE4A; EXOC1; CSNK1D; PPP2CB; GMFB; TMEM30A; UBE3B; KIAA1109; ZFP106; FAM134C; SFRS18; TMEM189- UBE2V1; TUBGCP2; ZZZ3; RPN2; C2orf28; ATP6AP2; UBE2D3; PAFAH1B1; UNC50; RP6-213H19.1; ARL8B; WIPF1; SSR4; WSB1; SERINC1; ZNF706; TM9SF1; GMPR2; ARF3; TMEM131; ZMYM4; ELMO2; RAB1A; ITFG1; TMEM59; HTRA2; C3orf63; HELZ; MAP2K1; ZDHHC7; MAPK14; MCM3AP; IL10RB; RHOT1; HERC1; VAMP3; CMTM6; GLOD4; CUL5; LAMP1; ISCU; RPN1; RNF111; VTI1B; PGK1; SCAMP1; PIGF; SFRS17A; ARHGAP1; SLC38A2; FOXJ3; TMEM49; ZDHHC17; FNTA; SPTLC1; BTAF1; ST13; TXNDC14; C15orf24; UBR4; GPBP1L1; TMEM111; GTF3C3; FTHP1; NT5C2; SMCHD1; DOCK2; TMEM39B; MRFAP1L1; NMT1; FRYL; UXT; GAK; PIGG; RBL2; KIDINS220; TRIM33; LRRC47; ACTR10; GGNBP2; ATP6AP1; TBC1D25; OSBPL2; MAPRE2; ROCK1; E2A-PBX1 SMARCA5 <0.001 0 - down 2500 570 NISCH; NUDT9; CDIPT; UBE2Z; ZFAND6; C19orf56; SFRS5; RNASEN; C5orf15;

Suppl. Table 3 – page 41

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PAPOLA; MDN1; C21orf66; VPS26A; TMEM1; KIAA0494; RAB6A; ATRX; DENR; PSMB5; EIF4A2; ASF1A; PIP4K2B; NDUFS4; NDUFB11; DMTF1; PPT1; TMEM123; FBXW4; SENP6; DCN; PI4KAP1; FBXL5; VAMP7; FOXK2; MTCH1; RNMT; TM9SF2; DCK; RAB7A; ARL1; PANK4; CUL4B; RAB6C; PJA2; METAP1; PNN; DCTN2; DERL2; SDF2; C19orf60; ANAPC13; DDX3X; HNRPA3P1; GPATCH8; ATP6V0C; CUL2; MSL-1; HISPPD1; PDHA1; GORASP2; RNF10; SEC63; TTC3; RCN2; ADAR; ZDHHC6; METT11D1; NMI; ZNF574; LASS2; PHF8; IRAK1BP1; NIF3L1; TLK1; PCNT; MPHOSPH9; HNRPH3; METTL3; SPEN; MAN1A2; SUB1; RAB2A; ZMPSTE24; MARK3; CYB5R3; ZNF294; MYST4; UBP1; RALBP1; RAB14; SON; ANAPC5; UTP3; BCAP31; DYRK1A; SAP30BP; TMEM147; ALG5; CBWD1; BAT1; PGS1; CNPY2; KIAA0265; SEC31A; BECN1; RBM26; FTSJ1; ZFR; ATP6V1H; KLHDC2; CANX; EBAG9; PCID2; PRKRIR; CAB39; PLEKHB2; ACSL3; MMS19; SUMO2; DNAJC13; HUWE1; PHF3; HNRPDL; VAPB; PMS1; C10orf76; NOLA3; SRF; SDCCAG1; C10orf6; ANAPC10; SMAD4; ALG8; SH3BGRL; RBM25; TXNDC15; SLC35A1; STARD7; LAGE3; VPS28; TMEM66; TARS; CSNK1A1; GMFG; NEK9; NOMO2; SEC24B; PGRMC1; SECISBP2; EIF2AK1; LIN37; ARMCX6; LOC130074; RRN3; TMEM208; MED13; DDX42; ZBTB1; ERCC5; USP9X; RABGGTB; ACIN1; RNF139; MED17; TCF25; DGCR2; NPEPPS; RBM39; RDH14; BRWD2; SS18L1; FAM21A; PSMD10; ZCCHC8; RPL36AL; RSRC2; RRP1B; PPIB; SLC30A5; TXNL4A; LAPTM4A; KIAA0196; DUS1L; TIAL1; C6orf211; SMC3; ATP6V1E1; QRICH1; SMARCA5; PHKB; DKC1; MARCH7; RNMTL1; ZNF518A; ALG6; INTS12; SSR1; TINAGL1; SLC22A5; ADCK2; DEPDC1; PLAC4; NEBL; HIST1H2BN; RALGPS2; CD19; BSPRY; ARL4A; ZNF528; DDR1; ZBTB6; ABCC4; TMEM63A; TAT; TPST1; KMO; OR7E38P; MYOZ2; TCL6; COL1A1; PARD6A; C6orf60; SLC35F5; NCF1; MPP6; ANKRD55; TRAK1; TULP4; VIPR2; CD9; ZNF669; ZNF257; RGS5; BCL9; VPREB3; BAMBI; BTK; EPAS1; ERO1LB; C14orf132; CDC14B; EHBP1L1; E2F2; SEMA6D; RASIP1; KCTD20; MUC5AC; CD24; ZNF771; MARCH3; FADS3; TCF4; PLGLB2; TERT; MLLT4; NR1D2; EGLN1; PHLDA2; GINS4; ENTPD3; HIST1H4C; CCDC69; BCAS4; LRP4; PRL; CLEC2D; VASH2; SPPL2B; AKAP12; SORT1; SPINT1; PCSK6; ITIH4; RNF144A; CPM; CRMP1; GJC1; FLJ13769; SLFN12; MLPH; E2F1; C6orf124; MYLK; AASS; DYRK3; TJP2; KCNJ2; C12orf32; BASP1; LOC91316; RAI14; AEBP1; E2F5; KCNJ3; RHOQ; SPA17; SNTB2; CEACAM21; IL8; CD84; FERMT1; FAM64A; CD48; PIP5K1B; VIPR1; SEMA5A; MDM4; PTTG3; ZSCAN16; PCSK5; LRIG1; PADI4; NINJ1; CD38; ITIH3; KIF13A; CD72; PAX5; NOTCH2; LRRN2; PLS3; FLJ20674; PDE4D; ALDH3A2; RHOB; ATRNL1; IGLL1; RHBDL2; GLDC; TRAK2; GPATCH2; RBBP5; ADAM19; TRIM16; AUTS2; C1orf135; NFATC4; BMPR2; IQSEC1; CELSR2; RAG2; ARHGAP8; TTC9; ST6GALNAC4; COBL; ZNF124; ARHGEF11; ZNF385D; TCF3; LOC90925; IL7R; SPAG6; SORBS2; MYT1L; MYL4; JAM2; PAWR; IGHM; COCH; GATM; WASF1;

Suppl. Table 3 – page 42

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PLXNB1; SH3PXD2A; PPFIBP1; KCNJ16; TNK2; MAP1A; BIK; FAM152A; VDR; TMSL8; CYFIP1; EMP2; P4HA2; BACH2; NRGN; KIAA0040; IL1B; PRR5; CORO2B; PPFIA4; ARNTL2; MAP3K1; PHACTR1; SH3BP4; CD58; EWSR1; FLI1; F13A1; TST; LTBP2; DOCK9; RHOBTB1; CASC1; TRIB2; TGFBR2; MAP1B; FGF9; GPR176; PSAT1; PIGZ; SLC15A2; CSF2RB; ODZ4; ENDOD1; D4S234E; QRSL1; TSSC1; GNAZ; KCNA3; ARHGEF9; FNDC3B; ALDH1A1; GALNT14; SYT1; TMEM121; KIAA0922; DOCK10; CALD1; RASAL1; ELOVL2; CCDC81; IL12RB2; IGSF3; APBB2; EAF2; KCNMB3; PLEKHF2; ELL3; BLK; IRF4; KIAA1305; AOX1; ROR1; SAMD4A; LRMP; PITPNC1; KANK1; ADARB1; DACT1; KCNJ12; FAM3C; GOLGA3; FAT; NCAPD3; NP; FHOD3; SORBS1; SEMA4C; SLAMF1; GP5; HIP1R; NID2; PRKCZ; KIAA0802; SYNPO; PSEN2; SLC27A2; MERTK; PBX1 LOC552891; HPRT1; PRDX3; NDUFA1; COX7B; FRG1; LAGE3; RBBP7; PSMC5; ARMET; UBE2A; ATPIF1; ATP5J; HMGN1; COPS6; UCRC; FLII; BCAP31; C21orf59; PECI; NDUFB8; CCDC56; ARL6IP1; COX6A1; RWDD1; PSMD2; PGAM1; MRPL13; PSMD4; MDH1; NDUFS1; PSMA3; HSPA5; MCTP2; GPHN; RIMS3; TP53TG3; CCR5; APOL6; GRIK2; RASL10A; PDE8B; TOX3; KAL1; HIP1; AKAP12; FLRT3; EFR3B; PRKG2; ABCB4; ZNF239; PTGDR; CD84; ZNF192; CSHL1; CDH11; ANGPT2; REEP1; FLT1; RAG2; LRRC8B; PCDH9; PCBP4; GLDC; RHBDL2; FER1L3; SLC6A16; AGMAT; TXNRD3; MPPED2; HEY2; Normal SMARCA5 <0.001 0 - down 1500 75 LHFPL2; STAP1; PTPRM; CENTG2 MGC29506; ZNF43; MYH10; AKAP12; ITPR3; HYI; HPS4; FAM65A; DBN1; MTF2; PBXIP1; PTP4A3; ALDH5A1; SCMH1; CDCA4; POGZ; RAB11A; NRN1; WSB2; RHBDF2; RHOQ; EHD4; RGS16; FOSL2; DUSP3; SPG20; FLT3; STARD13; VNN1; PSCDBP; P2RX5; PTGES3; RNASE6; SIDT2; C11orf24; CD44; GPM6B; MLL SMARCA4 <0.001 0 - down 400 44 SCPEP1; NLRP3; MAP7; LGALS1; KLRK1; CCNA1; C20orf103 DBN1; TUBB; SEPHS1; HRB; ANP32E; KIF20A; MYBL2; TIMELESS; ZNF675; MYH10; CDK2AP1; DCP1A; C11orf21; LGALS1; FAM13A1; S100A4; P2RX5; Relapse SMARCA4 <0.001 0 - down 1000 23 IDH1; NPR3; CD302; LTBR; CCPG1; TSPAN32 NME2; NOL14; CCDC86; FAM120A; C1QBP; LPXN; NIT2; DECR1; EEF1B2; GMDS; ACOT7; AMD1; BRP44L; FAM98A; TIMM13; DPP3; MRPL3; CTSC; APOO; MBD2; TTLL12; CASP4; GTPBP6; PPIF; PAICS; LETM1; ME2; PSD4; SRPRB; SRP72; WARS; ABCE1; OLA1; ICT1; C14orf108; MRLC2; PSMG2; LTA4H; C6orf66; NAT10; NPM1; NSF; C15orf15; UTP18; ZNF259; SRI; EIF2S1; EIF3M; HEATR3; RSU1; WDR43; PFKP; MRPS35; HADH; DHRS7; RPL26; SF3B5; PSMD9; HSP90AB1; IL2RG; TMEM109; KCNAB2; RABEPK; SF3A3; SRPK1; GART; NDUFV2; RAP2B; NOC3L; MRPS12; MTHFD2; LSM4; BTF3; ATIC; STRAP; APEX1; MRPS18B; C12orf10; IDE; PROSC; TADA3L; LRPPRC; DDX47; SMARCAL HINT1; MRPL23; TCP1; STARD7; SNRPD1; SLC7A1; MRPL9; APEH; R3HCC1; TEL-AML1 1 <0.001 0.04189 - down 2000 484 RPL10A; NUP98; MRPL4; HSPD1; RPIA; IMPDH2; POLR3E; MRPS2; ATP2C1;

Suppl. Table 3 – page 43

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

LGTN; LDHB; CLNS1A; NOL7; RPS27L; BZW2; CCDC53; FASTKD2; POLR2L; MRPS30; VPS4A; AGL; CUTA; UBA5; COX17; ADA; EIF2B2; C14orf166; GSTP1; RPL12; ATP5H; EBNA1BP2; PCM1; NDUFC1; PHB2; PIK3CB; TRAPPC6A; SHQ1; CCT2; GNL3; WDR3; GTF2A2; RPL13; SNRPE; APRT; FAH; PFN1; ITGAE; VAMP3; RPL35; USP20; ZNF32; C14orf156; MAPBPIP; TP53AP1; THOC7; IKBKAP; SLC3A2; EPRS; C12orf11; TXN; ETFB; SNRPF; HSP90AA1; LARP1; TDRD3; PARK7; LANCL1; PSMA4; UXT; WRB; WDR67; GCSH; AP2S1; TEX261; ANKRD27; RPL18; ALDOA; TTC19; ATP13A3; ATMIN; TIMM17A; FBL; SMYD3; COX8A; MDH2; RPS5; MTX1; DRAP1; POLR2H; NOLC1; PRKDC; OSTM1; SLC25A15; LOC730107; ENOPH1; TSFM; KIAA0152; DYNC1H1; TM2D3; PWP1; TOMM70A; EIF3I; C7orf24; DLAT; XPOT; CNIH; CLPP; TUFM; SMARCE1; WDR18; LEPROTL1; C11orf73; RRP1B; NOL11; BXDC5; NOLA2; CBFB; ATP6V1F; ASH2L; MIF; NOL1; TXNL1; C3orf28; HNRPAB; EIF3J; DLG3; SFMBT1; SUOX; SPP1; HEY2; SCARF1; TP63; CD74; KIAA0427; SP4; TMCC2; CSDA; SNX2; POU4F1; HIST1H2AG; MPL; CSF2RB; ALAS2; SLC35F2; PRSS7; ERAF; INPP5D; RP4-691N24.1; ZNF652; LAPTM5; FAIM3; GYPB; PCDH9; SCARB2; CRK; SOCS2; TCF4; C21orf7; ODZ4; HIST1H2AE; AGPAT2; MCTP2; ITIH3; PHTF1; OAS3; NRXN3; HLA-DOA; IGKV1OR2-108; DOK3; SLC4A1; LIN7B; HLA-DQB1; HLA-DRA; MAP4K2; ST8SIA4; IQCK; EPHB4; SH3TC1; TP53TG3; SMTN; KCTD7; IGHA1; CEBPE; LARGE; HLA-DPB1; MAMLD1; HLA- DPA1; AKAP12; MDM2; SCML2; HLA-DRB1; APBB1IP; DUSP26; FAM127B; GYPA; HIST1H2AJ; NPY; SERPINB9; HIST2H2AA3; IRAK3; INPPL1; CD52; GIMAP4; PFTK1; HIST1H2BI; TMEM140; HLA-DRB5; TNS3; CTGF; ALDOC; CACNA2D2; HIST2H2BE; E2F5; PTPRE; HIST1H2BE; WFS1; NCKAP1; DGCR6; TCL6; TCL1B; COBL; DYRK3; TXNIP; CHD7; CTNNA1; MYLK; GTDC1; SSX1; CLCN7; HIST1H2BG; HRK; HLA-DRB6; HIST1H2BH; SSX4; LRRN2; TRPV1; MEF2C; CD40; KANK2; CEACAM1; HPS4; EFEMP2; HLA-DMA; HLA-DMB; ZCCHC14; EFNA1; CRIM1; ATN1; PTPRG; CSF3R; tcag7.1314; MME; VPREB3; HHEX; CLCC1; UTRN; PDK1; SSX2; FADS3; ZNF274; MGC5370; RGL1; PYHIN1; NPR1; C12orf49; MYO5C; DIP2C; IL18RAP; FAM127A; IRS2; ERG; HIST1H2BF; NEIL1; CD79A; C1orf38; ZNF117; SIGLEC15; IL6ST; JUP; LPHN3; FGD6; CACNA1A; FGD1; TRIO; LILRA2; OCA2; MLXIP; LDOC1; GAB1; FLRT3; COL5A1; CHL1; SLC27A3; RALGPS1; PFKFB2; DPEP1; FHIT; POU2AF1; FOXO1; GTF2IRD1; INSR; SLC35E3; PTK2; FAM65A; BTN2A2; SCHIP1; ARHGAP24; EGFL7; PIK3IP1; C14orf132; ALOX5; NOL4; PRO2268; AK1; CCNJL; EPHA7; ISG20; BMP2; GNG7; ELK3; CKMT2; PSD3; LASS4; SOX11; TBC1D8B; EFNB2; STK32B; GPR17; DSC2; DUOX1; GABBR1; CRMP1; CACNB2; SPON1; EIF2AK3; ZNF91; MSR1; SDC1; KHDRBS3; NARFL; SMAD1; FERMT2; SEMA6A; SDC2; ARHGEF12; SCARB1; HLA-DOB; TBC1D9; ANGPTL2; H1F0; STAG3; DLGAP2; GNG11; SPTA1; CYB5R2; WDFY3; PID1; MAPK13; ABCG2; MDK; PLAG1;

Suppl. Table 3 – page 44

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

GREB1; C13orf18; PTP4A3; RAG1; FUCA1; NRN1; TRPM4; SEMA3F; TSPYL5; PDLIM7; TERF2; DRAM; PTPRK; MYO10; NR3C2; SPANXA1; KCNK3; GBA3; ARHGAP29; TNFRSF21; TMEM16A; LOC654342; NOVA1; HAP1; FBN2; TCFL5; TNS1; PCLO; BIRC7; CLIC5; ARHGEF4 GPATCH2; EWSR1; PIGB; ITPA; EFHA1; LOC51035; ELF1; PAIP1; SMARCA4; PDE8A; GADD45A; TPD52; SPTBN1; AKAP12; YLPM1; PSME4; NADK; TTC15; RPS6KA2; HPS4; ADAM17; STK39; SENP7; RNF41; SYK; NGLY1; OPN3; USP4; MOBKL3; GFPT1; LBA1; PTBP2; PAK2; VPS37B; MZF1; DKFZP564O0523; SMG1; SR140; LRP5L; UCKL1; ANKZF1; CAPN7; SSBP2; SFRS12; TSC2; TGFBR2; ADNP; DIP2C; C9orf45; STUB1; UBE2N; SNRP70; TERF1; FASTKD5; CLEC16A; C5orf5; ZNF586; ARID1A; CHP; SELT; BTG1; ZHX2; ZC3H7A; GNB1; Gcom1; SGSM3; MYO9B; IRF3; ATR; CCNL2; POU2F1; TMEM87A; ANKHD1; ARHGEF7; FUBP1; TWF1; TCL6; SFRS8; PIK3R1; TSSC1; ZMYND8; APC; FADS3; MARCH7; PPP6C; LOC440354; P2RX1; PRDM2; YTHDC2; NUDT4; F11R; TTC17; CUX1; RY1; UBA7; ING3; ROCK2; SLC7A5P1; DDEF2; ARPP-19; GABARAPL2; STK24; SLC25A36; MARS; SPSB3; SMPD4; PELI1; BZW1L1; RNASEH1; HNRPK; TTC13; TAPT1; CDC2L5; ZNF238; NFIL3; TMCC1; SLC35D1; LEMD3; HIATL1; C1orf80; ATP1B3; TRAK1; ATG12; SNX26; C1orf108; WEE1; SERTAD2; CGGBP1; ZNF12; LMF1; HNRNPA1; SF3B1; ARHGAP17; C3orf37; TCL1B; GTDC1; RBM5; ETHE1; SCNN1A; LY6E; COL18A1; AFG3L2; LAGE3; QDPR; TACC3; FAM45B; PTRH2; ALOX5AP; IL2RG; MAD2L1; EIF2AK2; FXYD6; PTTG1IP; EPHB3; KIAA1279; ITGB2; NUP214; GTF2H5; BEX4; TEX2; MED9; GPR132; USP18; ARMCX2; HRSP12; PGRMC2; IFI44; TIMP2; RFC1; HDAC2; APOO; IFI6; ENTPD6; IER3; ST7; DAPK1; ANKRD28; PWP2; TREML2; HSD17B8; E2F3; C16orf62; PDGFA; C4orf27; CFP; KIAA0513; PGRMC1; KIF4A; PLEKHA1; C11orf67; C1GALT1C1; CANT1; IMPA2; UBL4A; DYRK4; HERC6; C10orf119; GCN5L2; C17orf71; PRPS2; NEO1; GSTZ1; OAS1; ZNF516; FUT7; PSMG1; MICA; PLEK; KIAA1462; F2RL1; LSP1; ARMCX6; IL10RB; C21orf45; DLG5; EBP; NFE2; FAM26B; TK1; IL17RA; CSTB; NXT2; DDX60; MCTS1; TMEM165; ERCC6L; KIAA1166; TAF9B; VPS26A; ALDH6A1; SPIN2B; SUMO3; IFIT3; IFI44L; NDUFB11; H2AFY2; STCH; NGFR; PJA1; NSDHL; SUV39H1; TNNI2; CAMK1; CAPN2; UCHL5IP; CD1C; ORC3L; PLVAP; TIMM17B; TMEM164; PIN4; ACOT2; SLC19A1; CHAF1B; IFIT1; TMEM187; ASB9; POLA1; RBM47; C21orf33; PLCH1; PET112L; RRP1; RRP1B; DLG3; MGC39900; GPKOW; SOD1; CYBB; ECHDC3; PIP3-E; LYST; IL6R; EFNB1; PDXK; ARMCX1; MTCP1; PIGP; DHRS4; CEBPE; SH3BP5; PSMD10; Hyperdip>5 HCCS; ITSN1; MYBPC2; MS4A6A; TCEAL4; ADAM8; C10orf56; IL13RA1; 0 PRDM2 0.004 0 - down 1500 293 MORC4; IL3RA; ZNF185 PSMA7; MRPL34; COPS3; COX6C; NANS; AKR7A2; SCCPDH; UCRC; TIMM8B; Normal SMYD3 <0.001 0 - down 1500 72 ENSA; FH; HMGN3; MAPBPIP; TUBA1C; NDUFB8; ATP5G1; NDUFA6; NDUFS6;

Suppl. Table 3 – page 45

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

GPI; RAN; COX6A1; SFRS2B; INTS7; MRP63; PSMD2; SF3B5; TUBB2C; PGAM1; MRPL13; MDH1; NDUFS1; HSPA5; NDUFA8; PPP1R16B; TP53TG3; CCR5; MYLIP; APOL6; GRIK2; MXI1; RASL10A; PDE8B; EGFL7; AKAP12; GNG11; FLRT3; CHD7; EFR3B; PRKG2; ZNF239; PTGDR; CSHL1; RXRA; CDH11; LIG4; REEP1; FLT1; CASK; PCDH9; PCBP4; AP1B1; FER1L3; SLC6A16; AGMAT; PBX2; MPPED2; HEY2; CHST7; GFOD1; STAP1; PTPRM; CENTG2 SORD; CCDC86; FAM120A; C1QBP; NIT2; EIF4EBP1; DECR1; PTPN2; CABC1; ZNF593; GMDS; NME1; AMD1; BRP44L; FAM98A; TIMM13; DPP3; MRPL3; CTSC; ALDH9A1; TTLL12; ACAT2; PPIF; PAICS; FDX1; ATP5G1; SRPRB; SRP72; ABCE1; OLA1; UCHL5; WAPAL; C6orf66; NAT10; KLHL21; UTP18; ZNF259; SRI; EXOSC5; EIF3M; TFB2M; WDR43; PFKP; MRPS35; SF3B5; SF3A3; GART; NOC3L; MTHFD2; LSM4; ATIC; HSPC111; BRP44; NOC2L; STRAP; XTP3TPA; SNUPN; SLC1A4; UCHL3; LRPPRC; PLXNA3; HIST2H2BE; PTPRE; HIST1H2BE; WFS1; DGCR6; TCL6; TCL1B; TXNIP; CHD7; SSX1; HIST1H2BG; HRK; HLA-DRB6; HIST1H2BH; SSX4; CCR1; CD40; KANK2; CEACAM1; EFEMP2; HLA-DMA; HLA-DMB; AP1B1; EFNA1; CRIM1; PTPRG; tcag7.1314; MME; VPREB3; UTRN; SSX2; ST3GAL6; FADS3; MGC5370; RGL1; TSPAN14; NPR1; C12orf49; MYO5C; DIP2C; FAM127A; ERG; HIST1H2BF; NEIL1; CD79A; C1orf38; ZNF117; SIGLEC15; JUP; CLMN; LPHN3; MEST; CACNA1A; FGD1; LILRA2; MLXIP; LDOC1; GAB1; FLRT3; COL5A1; PXN; SLC27A3; DPEP1; FHIT; POU2AF1; FOXO1; INSR; SLC35E3; PTK2; FAM65A; BTN2A2; LTB; SCHIP1; ARHGAP24; EGFL7; PIK3IP1; ALOX5; NOL4; PRO2268; EPHA7; ISG20; BMP2; GNG7; ELK3; CKMT2; PSD3; LASS4; TBC1D8B; STK32B; GPR17; DSC2; DUOX1; GABBR1; ZNF91; SDC1; NARFL; SMAD1; FERMT2; SEMA6A; SCN3A; HLA-DOB; TBC1D9; H1F0; STAG3; DLGAP2; GNG11; SPTA1; WDFY3; PID1; MAPK13; MDK; C13orf18; PTP4A3; RAG1; FUCA1; TRPM4; SEMA3F; TSPYL5; TERF2; DRAM; PTPRK; NR3C2; SPANXA1; KCNK3; GBA3; ARHGAP29; TEL-AML1 SMYD3 <0.001 0 - down 750 195 TMEM16A; NOVA1; HAP1; FBN2; PCLO; BIRC7; CLIC5; ARHGEF4 NUCKS1; MRPL34; TRMT5; KIAA0101; TYMS; HMGN2; GSTP1; UCHL5IP; PSMC5; MAGOH; PSMB3; TBC1D25; ATP5J; PGD; HMGN1; COPS6; FLII; BCAP31; C21orf59; RCOR1; TUBA1C; MCM6; RFC4; PDIA6; CCDC56; EIF4A3; H2AFZ; CBX5; GPI; ARL6IP1; CKS1B; RAN; SFRS2B; SHMT1; PSMD2; TUBB2C; U2AF1; PSMD4; NDUFS1; PSMA3; AMT; MCTP2; TP53TG3; CCR5; APOL6; GRIK2; CBLB; PDE8B; TOX3; KAL1; FLRT3; EFR3B; PRKG2; ZNF239; CD84; ZNF192; CSHL1; RXRA; CDH11; ANGPT2; ITGA6; REEP1; FLT1; PRUNE2; RGS9; PCBP4; FER1L3; SLC6A16; AGMAT; TXNRD3; MPPED2; HEY2; LHFPL2; Normal EHMT2 <0.001 0 - down 1500 76 CHST7; STAP1; CENTG2 TRMT5; COX6C; RBX1; COX7B; HMGN2; PSMB3; ATPIF1; COPS6; UCRC; ENSA; TUBA1C; MCM6; NDUFB8; RFC4; H2AFZ; NDUFA6; NDUFS6; ARL6IP1; Normal CBX3 <0.001 0 - down 1500 56 RAN; COX6A1; SFRS2B; MRP63; PSMD2; SF3B5; PGAM1; MRPL13; MDH1;

Suppl. Table 3 – page 46

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

NDUFS1; TP53TG3; CCR5; MYLIP; APOL6; GRIK2; RASL10A; PDE8B; KAL1; FLRT3; CHD7; EFR3B; PRKG2; ABCB4; ZNF239; ZNF192; CSHL1; CDH11; ANGPT2; REEP1; FLT1; PCBP4; FER1L3; SLC6A16; AGMAT; PBX2; MPPED2; LHFPL2; GFOD1 NUCKS1; PSMA7; TRMT5; NDUFB2; COX6C; RBX1; TOR3A; MAGEF1; RNPEP; HMGN2; SS18L2; PSMB3; BID; UCRC; SYNJ2; RCOR1; MAPBPIP; CCNB2; TUBA1C; RPA3; HN1; CBX1; H2AFZ; NDUFA6; NDUFS6; CKS1B; COX6A1; SFRS2B; MRP63; PSMD2; SF3B5; FKSG30; MRPL13; NDUFS1; CD34; TP53TG3; MYLIP; MXI1; RASL10A; PDE8B; EGFL7; CHD7; EFR3B; PTGDR; ZNF192; CSHL1; CDH11; CREG1; ANGPT2; REEP1; FLT1; CAPN3; AGMAT; LGR5; PBX2; Normal CBX1 <0.001 0.02215 - down 500 60 HEY2; LHFPL2; GFOD1; STAP1; CENTG2 NDUFS5; GLUL; PNMA1; MAGEF1; PSMC6; COPS4; NDUFB8; SNRPN; GRIK5; Pseudodip CBX1 0.002 0 - down 1500 20 SSH3; HRK; ANXA4; SMC6; ERBB2; MPO; SERHL2; TAP2; TLE4; SLIT2; PALM TUBB; TOP2A; ARHGAP19; TPX2; SPAG5; MAGED1; ANP32E; KIF20A; CDC25B; CCNB2; BUB1; BIRC5; MAD2L1; AURKB; AKR1B1; KIF2C; H2AFZ; CDK2AP1; CKS1B; RAD51; C11orf21; CISH; CDC42EP3; NPR3; AMBRA1; Relapse CBX1 <0.001 0 - down 1500 33 LEPROT; PSTPIP2; FOXP1; LTBR; BAALC; FLJ13197; CCPG1; TSPAN32 DGKD; SETD1B; BCOR; CLASP2; ZEB2; ODC1; ULK1; ARL4A; WDR19; BCR; BCL7A; VLDLR; SLC5A3; MFAP3; LGMN; ST3GAL5; DAB2; LST1; YES1; SNX7; C11orf75; IFITM1; LARGE; CD52; MED9; PECAM1; CCR6; A2M; IFITM2; ABLIM1; EFNA1; ID3; BACE1; GPR56; FAM13A1; NLGN4X; ZNF467; DNTT; HLA-DQA1; XBP1; CEACAM6; TMEM156; DUSP26; CD34; SERPINB9; CAMSAP1L1; CEP68; ENPP2; OR7A5; MRC1; LXN; IGFBP4; GPR171; MYO5C; RBM47; NAV1; SLC35D2; TNFRSF14; SV2A; SCHIP1; SP140; FZD6; MYO1B; ARHGAP22; PDE9A; PHF15; ITGA6; CENTD1; IL2RA; LAMA3; C6orf32; BMPR1B; SERPINB6; GIMAP4; NT5E; MTSS1; ITGA5; SECTM1; CTNND1; FLJ14213; CCND2; APOL3; GLS; S100A13; OSBPL10; P2RY14; GIMAP6; RAPGEF3; EMP1; ARHGEF17; ASB13; FAM129A; PRX; IGJ; COL6A3; NPDC1; CASP10; CNN3; PSTPIP2; ECM1; SPARC; SLC2A5; TMEM204; LOC26010; BCR-ABL CBX4 <0.001 0 - down 750 108 OLFML2A; CTDSPL; NRP1; PON2 RNF40; EFHA1; ODC1; MCRS1; ELF1; H1FX; C1orf160; C9orf16; RER1; PSME4; NADK; RMND5A; PRKCSH; SF3A1; IQCC; USP4; VPS37B; MZF1; DDA1; BTBD2; RHOT2; NME3; SFRS12; TSC2; RHOBTB3; RGL1; FGD1; DLG5; CLEC4E; ERG; KIAA1166; EXDL2; IL1B; PPAP2B; MAGT1; OCRL; PECAM1; MRC1; STCH; NGFR; SAT1; CAPN2; LGMN; C10orf10; ASB9; MPP1; RBM47; Hyperdip>5 PLCH1; GSPT2; ALOX5; CYTL1; PIP3-E; SETBP1; PIGP; LOC57228; SH3BP5; 0 CBX4 <0.001 0 - down 500 59 ITSN1; TCEAL4; IL3RA BACH1; C4orf41; SIRT1; NUP54; RAB5A; TMEM164; COPS4; LAMP2; HNRPH2; Pseudodip MYST2 <0.001 0 - down 750 17 GRIK5; ATP1A3; GPR176; PCDH9; LMF1; COL9A3; AEBP1; SLIT2 E2A-PBX1 MYST3 <0.001 0 - down 1000 234 CIRBP; CTDSP2; KIAA0430; SERINC5; PRKCB1; AMZ2; STX16; SLC35E2; Suppl. Table 3 – page 47

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

C12orf35; DGAT1; STAT5B; CSNK1D; PPP2CB; C14orf159; GMFB; KIAA1109; RPS19; CBFA2T3; SFRS18; TMEM189-UBE2V1; ZZZ3; CLINT1; UBE2D3; C10orf18; ABCC1; PAFAH1B1; CLSTN1; UNC50; MBTPS1; PARC; RPL17; WSB1; ZNF706; SERTAD2; NARG1L; TMEM131; LOC388969; RAB1A; WASF2; TMEM59; HELZ; JMJD2B; ZDHHC7; FTL; MAPK14; MCM3AP; RHOT1; CHD9; HERC1; GDI1; CMTM6; VAV1; ZMYM1; NBPF1; ISCU; RNF111; CCNT2; ZMIZ1; FOXJ3; ZDHHC17; FNTA; MECP2; ST13; FOXN3; UBR4; FTH1; GPBP1L1; TMEM111; NT5C2; SMCHD1; SNX1; REL; MRFAP1L1; FRYL; MAP4K3; DPYSL2; GAK; BICD2; FKBP1A; MAGED2; KIDINS220; LRRC47; MYT1; ACTR10; GGNBP2; OSBPL2; MAPRE2; ROCK1; WDR37; NISCH; NUDT9; ZKSCAN1; UBE2Z; ZFAND6; SFRS5; RNASEN; TINAGL1; SLC22A5; ADCK2; PLAC4; NEBL; BSPRY; ZNF528; ATP1A3; TAT; NIP7; KMO; COL1A1; C6orf60; NCF1; ANKRD55; VIPR2; RGS5; UCK2; CDC14B; E2F2; SEMA6D; KCTD20; MUC5AC; MARCH3; TPR; PLGLB2; TERT; NR1D2; GINS4; ENTPD3; XYLT1; BCAS4; PRL; CLEC2D; SPPL2B; SORT1; PCSK6; RNF144A; CPM; EZR; MLPH; C6orf124; ADK; KCNJ2; BASP1; KCNJ3; RHOQ; IL8; CD84; FERMT1; CD48; CDKN2D; SEMA5A; MDM4; PTTG3; CXorf21; CD72; EIF2C3; GLDC; TRAK2; RBBP5; PLGLB1; KRAS; ADAM19; TRIM16; C1orf135; NFATC4; ARHGAP8; ST6GALNAC4; ZNF124; ARHGEF11; CSRP1; ZNF385D; TCF3; SPAG6; JAM2; IGHM; GATM; WASF1; SH3PXD2A; PPFIBP1; TNK2; BIK; SYNJ2; FAM152A; VDR; TMSL8; NRGN; PRR5; PPFIA4; ARNTL2; SRGAP2; MAP3K1; PHACTR1; EWSR1; F13A1; CASC1; TRIB2; MAP1B; FGF9; GPR176; PSAT1; PIGZ; SLC15A2; ENDOD1; GNAZ; KCNA3; ALDH1A1; GALNT14; SYT1; TMEM121; RASAL1; CCDC81; IL12RB2; APBB2; EAF2; ELL3; BLK; IRF4; KIAA1305; AOX1; ROR1; SAMD4A; LRMP; KANK1; ADARB1; DACT1; KCNJ12; NP; FHOD3; SLAMF1; GP5; KIAA0802; SYNPO; PSEN2; SLC27A2; MERTK; PBX1 PSMA7; MRPL34; TRMT5; NDUFB2; COPS3; COX6C; RBX1; HMGN2; AKR7A2; PSMB3; ATP5J; COPS6; UCRC; TIMM8B; HMGN3; MCM6; RPA3; RFC4; CCDC56; H2AFZ; NDUFA6; NDUFS6; RAN; COX6A1; SFRS2B; MRP63; PSMD2; MRPL13; PSMD4; MDH1; NDUFS1; PSMA3; TP53TG3; CCR5; MYLIP; APOL6; GRIK2; RASL10A; PDE8B; TOX3; KAL1; FLRT3; EFR3B; PRKG2; ZNF239; ZNF192; CSHL1; CDH11; ANGPT2; REEP1; FLT1; PCBP4; FER1L3; SLC6A16; AGMAT; TXNRD3; MPPED2; HEY2; LHFPL2; CHST7; GFOD1; STAP1; PTPRM; Normal HAT1 <0.001 0 - down 500 64 CENTG2 LOC552891; HPRT1; C16orf62; PRDX3; GOT1; DPYSL2; NDUFA1; PDHX; TRMT5; COX7B; FRG1; LAGE3; HMGN2; AIF1; SMS; RBBP7; PSMC5; UBE2A; ATPIF1; ATP5J; PGD; HMGN1; ARMCX1; UCRC; SOD1; BCAP31; RCOR1; HMGN3; PECI; NDUFB8; CCDC56; CD93; RWDD1; SLC9A6; PHB; PSMD4; FAM45B; PSMA3; NDUFA8; GPHN; RIMS3; TP53TG3; CCR5; APOL6; GRIK2; Normal MYST4 <0.001 0 - down 2000 84 CBLB; DLGAP4; RASL10A; PDE8B; TOX3; KAL1; HIP1; AKAP12; EFR3B;

Suppl. Table 3 – page 48

LP ESG p q Dir ESG.dys Opt.T O(T) GEMs(T)

PRKG2; ABCB4; ZNF239; PTGDR; CD84; ZNF192; APOBEC3G; CSHL1; ANGPT2; REEP1; RAG2; PRUNE2; LRRC8B; PCDH9; PCBP4; GLDC; RHBDL2; FER1L3; SLC6A16; CAPN3; AGMAT; LGR5; TXNRD3; MPPED2; LHFPL2; CHST7; CHST2; STAP1; PTPRM; CENTG2 BACH1; C4orf41; FAM45B; SIRT1; NUP54; RAB5A; PSMC6; LAMP2; TCEAL1; Pseudodip MYST4 <0.001 0 - down 500 16 HNRPH2; ATP1A3; GPR176; PCDH9; dJ222E13.2; AEBP1; SLIT2 MRPL34; TRMT5; RBX1; PSMC5; MAGOH; PSMB3; ATPIF1; PGD; COPS6; UCRC; FLII; ENSA; RCOR1; AHSA1; HN1; NDUFB8; RFC4; CCDC56; NDUFA6; NDUFS6; GPI; ARL6IP1; RAN; COX6A1; SFRS2B; MRP63; PSMD2; U2AF1; PSMD4; MDH1; NDUFS1; PSMA3; HSPA5; NDUFA8; MCTP2; CD34; GPHN; TP53TG3; CCR5; APOL6; GRIK2; CBLB; DLGAP4; RASL10A; PDE8B; TOX3; KAL1; HIP1; AKAP12; FLRT3; EFR3B; PRKG2; ABCB4; ZNF239; CD84; ZNF192; CSHL1; RXRA; CDH11; ANGPT2; ITGA6; REEP1; FLT1; PRUNE2; PCDH9; PCBP4; GLDC; FER1L3; SLC6A16; AGMAT; LGR5; PBX2; TXNRD3; MPPED2; Normal MYST1 <0.001 0 - down 2000 81 HEY2; LHFPL2; CHST7; GFOD1; STAP1; PTPRM; CENTG2 TRMT5; COX6C; TYMS; RBX1; HMGN2; PSMC5; PSMB3; ATPIF1; HMGN1; COPS6; UCRC; TUBA1C; MCM6; RPA3; HN1; NDUFB8; RFC4; CCDC56; H2AFZ; NDUFA6; NDUFS6; ARL6IP1; RAN; COX6A1; SFRS2B; MRP63; PSMD2; TUBB2C; PSMD4; MDH1; NDUFS1; CD34; TP53TG3; CCR5; APOL6; GRIK2; DLGAP4; PDE8B; KAL1; HIP1; EFR3B; PRKG2; ZNF239; ZNF192; CSHL1; CDH11; ANGPT2; REEP1; FLT1; FER1L3; SLC6A16; AGMAT; TXNRD3; Normal CTCF <0.001 0 - down 1000 56 MPPED2; LHFPL2; STAP1

Suppl. Table 3 – page 49

Supplementary Table 4

The significantly enriched GO items among the predicted GEMs that linking to phenotypes of interested

LP: Leukemia Phenotype ESG: Epigenetic Seed Gene MF: The GO ID for molecular function Description: The description of the GO ID #GO: The counts of Entrez Gene ids from the Hug133a array at each GO ID. #Int: The counts of the Genes co-Expressed with Mechanism genes (GEMs) annotated at each GO term. Un-adjusted P: The un-adjusted empirical vectorial enrichment p-value of every significant (p<0.001) “LP-ESG” pair q: The estimated false discovery rate (proportion of false positives incurred) at given empirical p-value threshold (Suppl. Methods). GEMs(200): The predicted GEMs using a parameter T=200.

LP-ESG MF Description #GO #Int Un- q GEMs(200) adjust ed P CD74; HLA-DRA; HLA-DRB1; BLNK; HLA- DPA1; HLA-DPB1; HLA-DMA; HLA-DRB5; CD79B; MEF2C; TCL1A; CD79A; SNX2; JUP; POU2AF1; TFEB; CHD7; GALNAC4S-6ST; HLA- DQB1; LAMC1; STX7; SLC27A3; PTPN18; HLA- T-ALL~DNMT3B DMB; BANK1; HLA-DRB6; PTK2; ENG; T-ALL~HDAC4 1.6e- tcag7.1314; HLA-F; FHL1; STK32B; SLC25A15; GO:0032395 MHC class II receptor activity 12 6 1.8e-9 BCR-ABL~DNMT3B 11 INSIG1; DSTN; HIRA; ZAP70; NOTCH3; BCR-ABL~HDAC4 MLLT11; C9orf78; VAT1; PELO; C14orf135; LZTFL1; CD247; NUCB2; PEX5; CHI3L2; NBR1; USP20; LAT; BCL11B; LCK; UBASH3A; MAL; CD3D; C5orf13; GLUL; JARID1B; MVP; STX3; GIMAP4; S100A13; MS4A1; RAPGEF3; TBXA2R; ECM1 GO:0005524 ATP binding 1067 14 3.5e-6 0.0002 TUBB; NCAPH; TOP2A; MKI67; TPX2; ANP32E; GO:0032559 adenyl ribonucleotide binding 1080 14 4.1e-6 0.0002 KIF20A; CCNB2; BUB1; CCNA2; AURKB; Relapse~CBX5 GO:0030554 adenyl nucleotide binding 1139 14 7.7e-6 0.0002 KIF2C; H2AFZ; CKS1B; ZWINT; NPR3; Relapse~DNMT3A GO:0032553 ribonucleotide binding 1328 15 8.9e-6 0.0002 FLJ13197; SHCBP1; ARHGAP19; KIF4A; SPAG5; Relapse~HDAC9 GO:0032555 purine ribonucleotide binding 1328 15 8.9e-6 0.0002 CDC45L; C21orf45; BIRC5; KIF11; PLK4; Relapse~ SUV39H1 GO:0017076 purine nucleotide binding 1389 15 1.5e-5 0.0003 TIMELESS; MAD2L1; RAD51; DBN1; SEPHS1; GO:0003774 motor activity 109 5 2.8e-5 0.0003 ZNF675; PRPF4B; S100A4; MYH10; SALL2;

Suppl. Table 4 – page 1 LP-ESG MF Description #GO #Int Un- q GEMs(200) adjust ed P

GO:0003777 microtubule motor activity 54 4 2.9e-5 0.0003 CEBPE; LGALS1; IGFBP7 GO:0000166 nucleotide binding 1596 15 8.2e-5 0.0008 GO:0004896 cytokine receptor activity 51 3 0.0019 0.0546 GO:0001875 lipopolysaccharide receptor 1 1 0.0049 0.0546 activity ELF1; ZNF75; ARMCX5; ASB9; ENOX2; UBE2A; GO:0051076 Gram-positive bacterium binding 1 1 0.0049 0.0546 ATP6AP2; MGC39900; MORC3; HNRPH2; GO:0019955 cytokine binding 81 3 0.0072 0.0546 PRKAR2B; WDR44; SOD1; SLC9A6; SETD3; GO:0004907 cytokine receptor activity 30 2 0.0094 0.0546 FTSJ1; ARMCX1; MTCP1; PIGP; LOC57228; Hyperdip>50~BAZ2A DHRS4; RP6-213H19.1; CRYZL1; PSMD10; GO:0001530 lipopolysaccharide binding 2 1 0.0098 0.0546 Hyperdip>50~CBX7 TCEAL1; TCEAL4; UPF3B; ECHDC3; ITSN1; GO:0003960 NADPH:quinone reductase 2 1 0.0098 0.0546 Hyperdip>50~HDAC6 MYBPC2; C10orf56; IL13RA1; IL3RA; ZNF185; activity Hyperdip>50~SMARC RAG2; ABCC4; AKAP12; PQBP1; CXorf45; GO:0004912 interleukin-3 receptor activity 2 1 0.0098 0.0546 A4 ABCD4; MAGEH1; LAS1L; RRP1B; GPKOW; GO:0004915 interleukin-6 receptor activity 2 1 0.0098 0.0546 ABCB7; UBQLN2; USP9X; RNF113A; MED12; GO:0015232 heme transporter activity 2 1 0.0098 0.0546 COMMD4; ANP32A; BCL2L1; SMARCA4; GO:0016404 15-hydroxyprostaglandin 2 1 0.0098 0.0546 SPTBN1; PSME4; HDGF; TLR2; IL6R; ALDH3B1; dehydrogenase (NAD+) activity MS4A6A; PLP2 GO:0019978 interleukin-3 binding 2 1 0.0098 0.0546 GO:0019981 interleukin-6 binding 2 1 0.0098 0.0546

Suppl. Table 4 - page 2

Supplementary Table 5

Robust GEMs and ESGs Predictive of Leukemia Relapse

- The robust 52 GEMs and 3 ESGs associating predictive of leukemia “relapse” that were identified with frequencies of occurrence of 95% or above in the 100 iterations of the three-fold cross- validation (Methods).

Probe Symbol Description GenBank UniGene

201105_at LGALS1 lectin, galactoside-binding, soluble, 1 (galectin 1) NM_002305 Hs.445351

201163_s_at IGFBP7 insulin-like growth factor binding protein 7 NM_001553 Hs.479808

201292_at TOP2A topoisomerase (DNA) II alpha 170kDa AL561834 Hs.156346

202377_at LEPROT leptin receptor overlapping transcript AW026535 Hs.705413

202626_s_at LYN v-yes-1 Yamaguchi sarcoma viral related oncogene homolog NM_002350 Hs.699154

202705_at CCNB2 cyclin B2 NM_004701 Hs.194698

202748_at GBP2 guanylate binding protein 2, interferon-inducible NM_004120 Hs.386567

202934_at HK2 hexokinase 2 AI761561 Hs.406266 Hs.591588

203005_at LTBR lymphotoxin beta receptor (TNFR superfamily, member 3) NM_002342 Hs.1116

203045_at NINJ1 ninjurin 1 NM_004148 Hs.494457

203145_at SPAG5 sperm associated antigen 5 NM_006461 Hs.514033

203186_s_at S100A4 S100 calcium binding protein A4 NM_002961 Hs.654444

203362_s_at MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast) NM_002358 Hs.591697

203434_s_at MME membrane metallo-endopeptidase AI433463 Hs.307734

204026_s_at ZWINT ZW10 interactor NM_007057 Hs.591363

204126_s_at CDC45L CDC45 cell division cycle 45-like (S. cerevisiae) NM_003504 Hs.474217

204444_at KIF11 kinesin family member 11 NM_004523 Hs.8878

208939_at SEPHS1 selenophosphate synthetase 1 AV682679 Hs.124027

208950_s_at ALDH7A1 aldehyde dehydrogenase 7 family, member A1 BC002515 Hs.483239

209026_x_at TUBB tubulin, beta AF141349 Hs.636480 Hs.706772 BUB1 budding uninhibited by benzimidazoles 1 homolog 209642_at BUB1 AF043294 Hs.469649 (yeast)

209715_at CBX5 chromobox homolog 5 (HP1 alpha homolog, Drosophila) L07515 Hs.632724

210052_s_at TPX2 TPX2, microtubule-associated, homolog (Xenopus laevis) AF098158 Hs.244580

212021_s_at MKI67 antigen identified by monoclonal antibody Ki-67 AU132185 Hs.80976

212372_at MYH10 myosin, heavy chain 10, non-muscle AK026977 Hs.16355

212386_at TCF4 transcription factor 4 BF592782 Hs.644653

212488_at COL5A1 collagen, type V, alpha 1 N30339 Hs.210283

212688_at PIK3CB phosphoinositide-3-kinase, catalytic, beta polypeptide BC003393 Hs.239818

212949_at NCAPH non-SMC condensin I complex, subunit H D38553 Hs.308045

213222_at PLCB1 phospholipase C, beta 1 (phosphoinositide-specific) AL049593 Hs.431173

213241_at PLXNC1 plexin C1 AF035307 Hs.584845

213283_s_at SALL2 sal-like 2 (Drosophila) BG285616 Hs.416358 Hs.169639 Hs.510812 213737_x_at GOLGA8G golgi autoantigen, golgin subfamily a, 8G AI620911 Hs.525714

213836_s_at WIPI1 WD repeat domain, phosphoinositide interacting 1 AW052084 Hs.463964

Suppl. Table 5 - page 1 Probe Symbol Description GenBank UniGene

213911_s_at H2AFZ H2A histone family, member Z BF718636 Hs.119192

215000_s_at FEZ2 fasciculation and elongation protein zeta 2 (zygin II) AL117593 Hs.258563

215221_at FOXP1 forkhead box P1 AK025064 Hs.431498

215239_x_at ZNF273 zinc finger protein 273 AU132789 Hs.520889 SWI/SNF related, matrix associated, actin dependent regulator 215714_s_at SMARCA4 AF254822 Hs.327527 of chromatin, subfamily a, member 4

216026_s_at POLE polymerase (DNA directed), epsilon AL080203 Hs.524871 Hs.657680

216548_x_at HMG4L high-mobility group (nonhistone chromosomal) protein 4-like AL049709 Hs.558624

217025_s_at DBN1 drebrin 1 AL110225 Hs.130316

217028_at CXCR4 chemokine (C-X-C motif) receptor 4 AJ224869 Hs.593413

217547_x_at ZNF675 zinc finger protein 675 BF308250 Hs.264345

218355_at KIF4A kinesin family member 4A NM_012310 Hs.648326

218457_s_at DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha NM_022552 Hs.515840

218755_at KIF20A kinesin family member 20A NM_005733 Hs.73625

219036_at CEP70 centrosomal protein 70kDa NM_024491 Hs.531962

219493_at SHCBP1 SHC SH2-domain binding protein 1 NM_024745 Hs.123253 natriuretic peptide receptor C/guanylate cyclase C 219789_at NPR3 AI628360 Hs.237028 Hs.619466 (atrionatriuretic peptide receptor C)

219871_at FLJ13197 hypothetical FLJ13197 NM_024614 Hs.29725

219978_s_at NUSAP1 nucleolar and spindle associated protein 1 NM_018454 Hs.615092

220416_at ATP8B4 ATPase, class I, type 8B, member 4 NM_024837 Hs.511311

220560_at C11orf21 chromosome 11 open reading frame 21 NM_014144 Hs.559181 acidic (leucine-rich) nuclear phosphoprotein 32 family, 221505_at ANP32E AW612574 Hs.656466 member E

Suppl. Table 5 - page 2

Supplementary Table 6

Previously reported facts about predicted GEMs - The overlap of our predicted GEMs with reported marker genes for leukemia “Hyperdip>50” (Ross, Zhou et al. 2003) was tested in the first three rows. - The following rows in the table list the details of the corresponding GEMs.

Probe-sets: The probe-set ID that Affymetrix used for Hgu133a array Symbol: Symbol of gene Description: Description of gene UniGene: Unigene ID of gene ES G. d y s : The average change of ESG in expression to “Hyperdip>50” compared to other phenotypes. HDAC6: “Y” annotates the GEMs that associate to “HDAC6-Hyperdip>50” linkage as well were reported by Ross et al as Hyperdip>50 markers. BAZ2A: “Y” annotates the GEMs that associate to “BAZ2A-Hyperdip>50” linkage as well were reported by Ross et al as Hyperdip>50 markers. Decision: Genes also in the top 100 chi-square probe-sets selected for Hyperdip>50 in decision tree format that was reported by the data author (Ross, Zhou et al. 2003). Parallel: Genes also in the top 100 chi-square probe-sets selected for Hyperdip>50 in parallel format that was reported by the data author (Ross, Zhou et al. 2003).

Probe-sets Symbol Description UniGene GEMs. HDAC6 BAZ2A Decision Parallel dys #overlapping 24 28 17 25 Fisher’s test 124 196 58 139 ratio Fisher’s test p <2x10-16 <2x10-16 <2x10-16 <2x10-16 212420_at ELF1 E74-like factor 1 (ets domain transcription factor) Hs.135646 down Y 213659_at ZNF75 zinc finger protein 75 (D8C6) Hs.533540 up Y Hs.667773 205673_s_at ASB9 ankyrin repeat and SOCS box-containing 9 Hs.19404 up Y

Suppl. Table 6 - page 1 Probe-sets Symbol Description UniGene GEMs. HDAC6 BAZ2A Decision Parallel dys

204643_s_at ENOX2 Ecto-NOX disulfide-thiol exchanger 2 Hs.171458 up Y 214051_at MGC39900 hypothetical protein MGC39900 Hs.496530 up Y Y Hs.675540 203680_at PRKAR2B protein kinase, cAMP-dependent, regulatory, type II, beta Hs.433068 up Y Y 219297_at WDR44 WD repeat domain 44 Hs.98510 up Y Y 200642_at SOD1 superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) Hs.443914 up Y Y Y 212465_at SETD3 SET domain containing 3 Hs.510407 up Y 218694_at ARMCX1 armadillo repeat containing, X--linked 1 Hs.9728 up Y Y Y

216862_s_at MTCP1 mature T-cell proliferation 1 Hs.6917 up Y 221689_s_at PIGP phosphatidylinositol glycan anchor biosynthesis, class P Hs.656565 up Y Y 209679_s_at LOC57228 small trans-membrane and glycosylated protein Hs.652389 up Y Y 218021_at DHRS4 dehydrogenase/reductase (SDR family) member 4 Hs.528385 up Y Y 219767_s_at CRYZL1 crystallin, zeta (quinone reductase)-like 1 Hs.352671 up Y 204045_at TCEAL1 transcription elongation factor A (SII)-like 1 Hs.605138 up Y Y 202371_at TCEAL4 transcription elongation factor A (SII)-like 4 Hs.194329 up Y Y 219335_at ARMCX5 armadillo repeat containing, X-linked 5 Hs.522729 up Y Y

201899_s_at UBE2A Ubiquitin-conjugating enzyme E2A (RAD6 homolog) Hs.379466 up Y Y Y Y 201443_s_at ATP6AP2* ATPase, H+ transporting, lysosomal accessory protein 2 Hs.495960 up Y Y Y Y 213000_at MORC3 MORC family CW-type zinc finger 3 Hs.421150 up Y Y Y 201132_at HNRPH2 heterogeneous nuclear ribonucleoprotein H2 (H') Hs.632828 up Y Y Y Y 213289_at PA2G4 Proliferation-associated 2G4, 38kDa Hs.524498 up Y Y Y Hs.573018 203909_at SLC9A6 solute carrier family 9 (sodium/hydrogen exchanger), member 6 Hs.62185 up Y Y Y

Suppl. Table 6 - page 2

Probe-sets Symbol Description UniGene GEMs. HDAC6 BAZ2A Decision Parallel dys

205324_s_at FTSJ1* FtsJ homolog 1 (E. coli) Hs.23170 up Y Y Y Y 218499_at RP6-213H1 serine/threonine protein kinase MST4 Hs.444247 up Y Y Y Y 9.1 219485_s_at PSMD10 proteasome (prosome, macropain) 26S subunit, non ATPase, 10 Hs.522752 up Y Y Y Y 218757_s_at UPF3B UPF3 regulator of nonsense transcripts homolog B (yeast) Hs.103832 up Y Y Y Y 215117_at RAG2 recombination activating gene 2 Hs.159376 down Y Y 203196_at ABCC4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 Hs.508423 down Y 210517_s_at AKAP12 A kinase (PRKA) anchor protein (gravin) 12 Hs.371240 down Y 205583_s_at CXorf45 chromosome X open reading frame 45 Hs.110853 up Y Hs.443061 203981_s_at ABCD4 ATP-binding cassette, sub-family D (ALD), member 4 Hs.94395 up Y 218573_at MAGEH1* melanoma antigen family H, 1 Hs.279819 up Y Y 208117_s_at LAS1L LAS1-like (S. cerevisiae) Hs.522675 up Y Y 212846_at RRP1B ribosomal RNA processing 1 homolog B (S. cerevisiae) Hs.654727 up Y 203776_at GPKOW G patch domain and KOW motifs Hs.503666 up Y Y 209620_s_at ABCB7 ATP-binding cassette, sub-family B (MDR/TAP), member 7 Hs.370480 up Y Y 215884_s_at UBQLN2 ubiquilin 2 Hs.179309 up Y Y 201100_s_at USP9X ubiquitin specific peptidase 9, X-linked Hs.77578 up Y Y Y 209565_at RNF113A ring finger protein 113A Hs.458365 up Y Y Y 216071_x_at MED12 mediator complex subunit 12 Hs.409226 up Y Y Y *: Genes that are known as x-linked mental retardation markers (Ross, Zhou et al. 2003).

Suppl. Table 6 - page 3

Supplementary Table 7

Comparison GEMs in PGnet with genes identified by ARACNE

Phenotype Co-expressed genes Reversed co-expressed genes BCR-ABL DNMT3B* HDAC4* CBX1* E2A-PBX1 PHLDA2 CBX6 BAZ2B MYST4* MYST2 MCEP2* SMARCA2 HDAC7A Hyperdip>50 HDAC6 BAZ2A SMARCA4* SMARCC2 MLL DNMT3B HDAC9 CBX4 SMARCA2 SMYD3* Normal IGF2 SUV39H1 CBX5* MYST4* Pseudodip SMARCD2 T-ALL BAZ2B DNMT3B* HDAC5 SMARCD2 SMARCA2 PRDM2 HDAC4* MARCAL1 SMYD3* CBX1* TEL-AML1 MECP2* PRDM2 MBD2* HDAC9 2nd_AML CBX6 CCR CBX6 HDAC9 Relapse SUV39H1 CBX5* *GEMs in direct-transcriptional regulation network according to ARACNE.

Suppl. Table 7 - page 1

Supplementary Table 8

Comparison of the results from ARACNE and PGnet for leukemia phenotypes

LP: Leukemia Phenotype ESG: Epigenetic Seed Gene ARACNE: The number of predicted genes by ARACNE that associated with corresponding ESG in samples in the corresponding LP. PGnet: The number of predicted genes by PGnet that associated with corresponding ESG in samples in the corresponding LP. Intersection: The number of genes that predicted by both ARACNE and PGnet Lowest rank The lowest rank of multiple information (MI) estimated by ARACNE for “intersection” genes. Highest rank: The highest rank of multiple information (MI) estimated by ARACNE for “intersection” genes.

LP ESG ARACNE PGnet Intersection Lowest rank Highest rank Relapse CBX5 857 17 7 511 807 SUV39H1 1241 22 6 294 983 DNMT3A 893 6 4 38 681 HDAC9 1158 5 3 13 199 Normal CBX5 795 16 4 5 78 SUV39H1 740 23 3 16 729 CCR HDAC9 1284 13 10 14 768 MLL HDAC9 684 51 3 364 662 SMARCA2 684 31 4 79 639 TEL-AML1 HDAC9 >1172 47 5 109 1151 DNMT3A 694 25 3 80 530 MBD2 >1172 20 2 103 475 Hyperdip>50 HDAC6 >1128 25 >14 55 1015 SMARCA4 >1128 17 >5 248 1049 CBX7 1024 7 2 50 250 BAZ2A >1128 27 >6 267 974 Pseudodip BAZ2A 1321 9 3 42 826 BCR-ABL DNMT3B 963 12 3 570 866 HDAC4 923 31 3 51 501 CBX1 1047 25 1 770 T-ALL DNMT3B 904 40 2 343 826 HDAC4 >1229 56 >14 25 1037 SMYD3 119 17 0 HDAC5 >1229 25 >4 113 1037 PRDM2 974 30 4 72 883 E2A-PBX1 CBX6 659 21 2 335 493 MECP2 937 33 2 108 663 PHLDA2 >1021 34 >7 73 1002 BAZ2B >1021 45 11 22 962 HDAC7 >1021 38 >4 635 1011 SMARCA2 718 30 5 483 716 MYST2 474 26 0 MYST4 >1021 19 >2 727 909

Suppl. Table 8 - page 1