Molecular Features of Triple Negative Breast Cancer Cells by Genome-Wide Gene Expression Profiling Analysis
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Aurora B-Dependent Ndc80 Degradation Regulates
bioRxiv preprint doi: https://doi.org/10.1101/836668; this version posted November 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Aurora B-dependent Ndc80 Degradation Regulates Kinetochore Composition in 2 Meiosis 3 4 5 Running title: Aurora B Regulates Ndc80 Proteolysis in Meiosis 6 7 Keywords: meiosis, kinetochore, Aurora B, Ndc80, chromosome, proteolysis, APC 8 9 10 Jingxun Chen1, Andrew Liao1, Emily N Powers1, Hanna Liao1, Lori A Kohlstaedt2, Rena 11 Evans3, Ryan M Holly1, Jenny Kim Kim4, Marko Jovanovic4 and Elçin Ünal1, § 12 13 1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 14 94720, United States 15 2 UC Berkeley QB3 Proteomics Facility, University of California, Berkeley, CA 94720, 16 United States 17 3 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States 18 4 Department of Biology, Columbia University, New York City, NY 10027, United States 19 20 § Correspondence: [email protected] 21 22 23 24 25 26 1 bioRxiv preprint doi: https://doi.org/10.1101/836668; this version posted November 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 27 ABSTRACT 28 29 The kinetochore complex is a conserved machinery that connects chromosomes to 30 spindle microtubules. -
Genome Sequence, Population History, and Pelage Genetics of the Endangered African Wild Dog (Lycaon Pictus) Michael G
Campana et al. BMC Genomics (2016) 17:1013 DOI 10.1186/s12864-016-3368-9 RESEARCH ARTICLE Open Access Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus) Michael G. Campana1,2*, Lillian D. Parker1,2,3, Melissa T. R. Hawkins1,2,3, Hillary S. Young4, Kristofer M. Helgen2,3, Micaela Szykman Gunther5, Rosie Woodroffe6, Jesús E. Maldonado1,2 and Robert C. Fleischer1 Abstract Background: The African wild dog (Lycaon pictus) is an endangered African canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage. Results: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection. Conclusions: We show that the African wild dog has undergone at least two effective population size reductions in the last 1,000,000 years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage. Keywords: Lycaon pictus, Genome, Population history, Selection, Pelage Background Primarily a hunter of antelopes, the African wild dog is a The African wild dog (Lycaon pictus) is an endangered highly distinct canine. -
Kinesin Family Member 18B Regulates the Proliferation and Invasion Of
Wu et al. Cell Death and Disease (2021) 12:302 https://doi.org/10.1038/s41419-021-03582-2 Cell Death & Disease ARTICLE Open Access Kinesin family member 18B regulates the proliferation and invasion of human prostate cancer cells Yu-Peng Wu 1,Zhi-BinKe 1, Wen-Cai Zheng 1, Ye-Hui Chen 1,Jun-MingZhu 1,FeiLin 1,Xiao-DongLi 1, Shao-Hao Chen 1,HaiCai 1, Qing-Shui Zheng 1, Yong Wei 1, Xue-Yi Xue 1 and Ning Xu 1 Abstract Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K–AKT–mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K–AKT–mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role – – 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; in PCa via activation of the PI3K AKT mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa. -
Screening of a Clinically and Biochemically Diagnosed SOD Patient Using Exome Sequencing: a Case Report with a Mutations/Variations Analysis Approach
The Egyptian Journal of Medical Human Genetics (2016) 17, 131–136 HOSTED BY Ain Shams University The Egyptian Journal of Medical Human Genetics www.ejmhg.eg.net www.sciencedirect.com CASE REPORT Screening of a clinically and biochemically diagnosed SOD patient using exome sequencing: A case report with a mutations/variations analysis approach Mohamad-Reza Aghanoori a,b,1, Ghazaleh Mohammadzadeh Shahriary c,2, Mahdi Safarpour d,3, Ahmad Ebrahimi d,* a Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran b Research and Development Division, RoyaBioGene Co., Tehran, Iran c Department of Genetics, Shahid Chamran University of Ahvaz, Ahvaz, Iran d Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Received 12 May 2015; accepted 15 June 2015 Available online 22 July 2015 KEYWORDS Abstract Background: Sulfite oxidase deficiency (SOD) is a rare neurometabolic inherited disor- Sulfite oxidase deficiency; der causing severe delay in developmental stages and premature death. The disease follows an auto- Case report; somal recessive pattern of inheritance and causes deficiency in the activity of sulfite oxidase, an Exome sequencing enzyme that normally catalyzes conversion of sulfite to sulfate. Aim of the study: SOD is an underdiagnosed disorder and its diagnosis can be difficult in young infants as early clinical features and neuroimaging changes may imitate some common diseases. Since the prognosis of the disease is poor, using exome sequencing as a powerful and efficient strat- egy for identifying the genes underlying rare mendelian disorders can provide important knowledge about early diagnosis, disease mechanisms, biological pathways, and potential therapeutic targets. -
0.5) in Stat3∆/∆ Compared with Stat3flox/Flox
Supplemental Table 2 Genes down-regulated (<0.5) in Stat3∆/∆ compared with Stat3flox/flox Probe ID Gene Symbol Gene Description Entrez gene ID 1460599_at Ermp1 endoplasmic reticulum metallopeptidase 1 226090 1460463_at H60c histocompatibility 60c 670558 1460431_at Gcnt1 glucosaminyl (N-acetyl) transferase 1, core 2 14537 1459979_x_at Zfp68 zinc finger protein 68 24135 1459747_at --- --- --- 1459608_at --- --- --- 1459168_at --- --- --- 1458718_at --- --- --- 1458618_at --- --- --- 1458466_at Ctsa cathepsin A 19025 1458345_s_at Colec11 collectin sub-family member 11 71693 1458046_at --- --- --- 1457769_at H60a histocompatibility 60a 15101 1457680_a_at Tmem69 transmembrane protein 69 230657 1457644_s_at Cxcl1 chemokine (C-X-C motif) ligand 1 14825 1457639_at Atp6v1h ATPase, H+ transporting, lysosomal V1 subunit H 108664 1457260_at 5730409E04Rik RIKEN cDNA 5730409E04Rik gene 230757 1457070_at --- --- --- 1456893_at --- --- --- 1456823_at Gm70 predicted gene 70 210762 1456671_at Tbrg3 transforming growth factor beta regulated gene 3 21378 1456211_at Nlrp10 NLR family, pyrin domain containing 10 244202 1455881_at Ier5l immediate early response 5-like 72500 1455576_at Rinl Ras and Rab interactor-like 320435 1455304_at Unc13c unc-13 homolog C (C. elegans) 208898 1455241_at BC037703 cDNA sequence BC037703 242125 1454866_s_at Clic6 chloride intracellular channel 6 209195 1453906_at Med13l mediator complex subunit 13-like 76199 1453522_at 6530401N04Rik RIKEN cDNA 6530401N04 gene 328092 1453354_at Gm11602 predicted gene 11602 100380944 1453234_at -
1 AGING Supplementary Table 2
SUPPLEMENTARY TABLES Supplementary Table 1. Details of the eight domain chains of KIAA0101. Serial IDENTITY MAX IN COMP- INTERFACE ID POSITION RESOLUTION EXPERIMENT TYPE number START STOP SCORE IDENTITY LEX WITH CAVITY A 4D2G_D 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ B 4D2G_E 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ C 6EHT_D 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ D 6EHT_E 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ E 6GWS_D 41-72 41 72 100 100 3.2Å PCNA X-RAY DIFFRACTION √ F 6GWS_E 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ G 6GWS_F 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ H 6IIW_B 2-11 2 11 100 100 1.699Å UHRF1 X-RAY DIFFRACTION √ www.aging-us.com 1 AGING Supplementary Table 2. Significantly enriched gene ontology (GO) annotations (cellular components) of KIAA0101 in lung adenocarcinoma (LinkedOmics). Leading Description FDR Leading Edge Gene EdgeNum RAD51, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, CENPW, HJURP, NDC80, CDCA5, NCAPH, BUB1, ZWILCH, CENPK, KIF2C, AURKA, CENPN, TOP2A, CENPM, PLK1, ERCC6L, CDT1, CHEK1, SPAG5, CENPH, condensed 66 0 SPC24, NUP37, BLM, CENPE, BUB3, CDK2, FANCD2, CENPO, CENPF, BRCA1, DSN1, chromosome MKI67, NCAPG2, H2AFX, HMGB2, SUV39H1, CBX3, TUBG1, KNTC1, PPP1CC, SMC2, BANF1, NCAPD2, SKA2, NUP107, BRCA2, NUP85, ITGB3BP, SYCE2, TOPBP1, DMC1, SMC4, INCENP. RAD51, OIP5, CDK1, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, ESCO2, CENPW, HJURP, TTK, NDC80, CDCA5, BUB1, ZWILCH, CENPK, KIF2C, AURKA, DSCC1, CENPN, CDCA8, CENPM, PLK1, MCM6, ERCC6L, CDT1, HELLS, CHEK1, SPAG5, CENPH, PCNA, SPC24, CENPI, NUP37, FEN1, chromosomal 94 0 CENPL, BLM, KIF18A, CENPE, MCM4, BUB3, SUV39H2, MCM2, CDK2, PIF1, DNA2, region CENPO, CENPF, CHEK2, DSN1, H2AFX, MCM7, SUV39H1, MTBP, CBX3, RECQL4, KNTC1, PPP1CC, CENPP, CENPQ, PTGES3, NCAPD2, DYNLL1, SKA2, HAT1, NUP107, MCM5, MCM3, MSH2, BRCA2, NUP85, SSB, ITGB3BP, DMC1, INCENP, THOC3, XPO1, APEX1, XRCC5, KIF22, DCLRE1A, SEH1L, XRCC3, NSMCE2, RAD21. -
Real-Time Dynamics of Plasmodium NDC80 Reveals Unusual Modes of Chromosome Segregation During Parasite Proliferation Mohammad Zeeshan1,*, Rajan Pandey1,*, David J
© 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2021) 134, jcs245753. doi:10.1242/jcs.245753 RESEARCH ARTICLE SPECIAL ISSUE: CELL BIOLOGY OF HOST–PATHOGEN INTERACTIONS Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation Mohammad Zeeshan1,*, Rajan Pandey1,*, David J. P. Ferguson2,3, Eelco C. Tromer4, Robert Markus1, Steven Abel5, Declan Brady1, Emilie Daniel1, Rebecca Limenitakis6, Andrew R. Bottrill7, Karine G. Le Roch5, Anthony A. Holder8, Ross F. Waller4, David S. Guttery9 and Rita Tewari1,‡ ABSTRACT eukaryotic organisms to proliferate, propagate and survive. During Eukaryotic cell proliferation requires chromosome replication and these processes, microtubular spindles form to facilitate an equal precise segregation to ensure daughter cells have identical genomic segregation of duplicated chromosomes to the spindle poles. copies. Species of the genus Plasmodium, the causative agents of Chromosome attachment to spindle microtubules (MTs) is malaria, display remarkable aspects of nuclear division throughout their mediated by kinetochores, which are large multiprotein complexes life cycle to meet some peculiar and unique challenges to DNA assembled on centromeres located at the constriction point of sister replication and chromosome segregation. The parasite undergoes chromatids (Cheeseman, 2014; McKinley and Cheeseman, 2016; atypical endomitosis and endoreduplication with an intact nuclear Musacchio and Desai, 2017; Vader and Musacchio, 2017). Each membrane and intranuclear mitotic spindle. To understand these diverse sister chromatid has its own kinetochore, oriented to facilitate modes of Plasmodium cell division, we have studied the behaviour movement to opposite poles of the spindle apparatus. During and composition of the outer kinetochore NDC80 complex, a key part of anaphase, the spindle elongates and the sister chromatids separate, the mitotic apparatus that attaches the centromere of chromosomes to resulting in segregation of the two genomes during telophase. -
Expression of the POTE Gene Family in Human Ovarian Cancer Carter J Barger1,2, Wa Zhang1,2, Ashok Sharma 1,2, Linda Chee1,2, Smitha R
www.nature.com/scientificreports OPEN Expression of the POTE gene family in human ovarian cancer Carter J Barger1,2, Wa Zhang1,2, Ashok Sharma 1,2, Linda Chee1,2, Smitha R. James3, Christina N. Kufel3, Austin Miller 4, Jane Meza5, Ronny Drapkin 6, Kunle Odunsi7,8,9, 2,10 1,2,3 Received: 5 July 2018 David Klinkebiel & Adam R. Karpf Accepted: 7 November 2018 The POTE family includes 14 genes in three phylogenetic groups. We determined POTE mRNA Published: xx xx xxxx expression in normal tissues, epithelial ovarian and high-grade serous ovarian cancer (EOC, HGSC), and pan-cancer, and determined the relationship of POTE expression to ovarian cancer clinicopathology. Groups 1 & 2 POTEs showed testis-specifc expression in normal tissues, consistent with assignment as cancer-testis antigens (CTAs), while Group 3 POTEs were expressed in several normal tissues, indicating they are not CTAs. Pan-POTE and individual POTEs showed signifcantly elevated expression in EOC and HGSC compared to normal controls. Pan-POTE correlated with increased stage, grade, and the HGSC subtype. Select individual POTEs showed increased expression in recurrent HGSC, and POTEE specifcally associated with reduced HGSC OS. Consistent with tumors, EOC cell lines had signifcantly elevated Pan-POTE compared to OSE and FTE cells. Notably, Group 1 & 2 POTEs (POTEs A/B/B2/C/D), Group 3 POTE-actin genes (POTEs E/F/I/J/KP), and other Group 3 POTEs (POTEs G/H/M) show within-group correlated expression, and pan-cancer analyses of tumors and cell lines confrmed this relationship. Based on their restricted expression in normal tissues and increased expression and association with poor prognosis in ovarian cancer, POTEs are potential oncogenes and therapeutic targets in this malignancy. -
Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes
Tohoku J. Exp. Med., 2011,Differential 223, 161-176 Gene Expression in OPCs, Oligodendrocytes and Type II Astrocytes 161 Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes Jian-Guo Hu,1,2,* Yan-Xia Wang,3,* Jian-Sheng Zhou,2 Chang-Jie Chen,4 Feng-Chao Wang,1 Xing-Wu Li1 and He-Zuo Lü1,2 1Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China 2Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China 3Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China 4Department of Laboratory Medicine, Bengbu Medical College, Bengbu, P.R. China Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. -
Microrna-7-5P Mediates the Signaling of Hepatocyte Growth
www.nature.com/scientificreports OPEN MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the Received: 30 August 2017 Accepted: 2 November 2017 MCF-10A mammary epithelial cell Published: xx xx xxxx Dawoon Jeong1, Juyeon Ham1, Sungbin Park1, Seungyeon Lee 1, Hyunkyung Lee1, Han-Sung Kang2 & Sun Jung Kim1 MicroRNA-7 (miR-7) is a non-coding RNA of 23-nucleotides that has been shown to act as a tumor suppressor in various cancers including breast cancer. Although there have been copious studies on the action mechanisms of miR-7, little is known about how the miR is controlled in the mammary cell. In this study, we performed a genome-wide expression analysis in miR-7-transfected MCF-10A breast cell line to explore the upstream regulators of miR-7. Analysis of the dysregulated target gene pool predicted hepatocyte growth factor (HGF) as the most plausible upstream regulator of miR-7. MiR-7 was upregulated in MCF-10A cells by HGF, and subsequently downregulated upon treatment with siRNA against HGF. However, the expression of HGF did not signifcantly change through either an upregulation or downregulation of miR-7 expression, suggesting that HGF acts upstream of miR-7. In addition, the target genes of miR-7, such as EGFR, KLF4, FAK, PAK1 and SET8, which are all known oncogenes, were downregulated in HGF-treated MCF-10A; in contrast, knocking down HGF recovered their expression. These results indicate that miR-7 mediates the activity of HGF to suppress oncogenic proteins, which inhibits the development of normal cells, at least MCF-10A, into cancerous cells. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Gene Co-Expression Network Mining Using Graph Sparsification
Gene Co-expression Network Mining Using Graph Sparsification THESIS Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Jinchao Di Graduate Program in Electrical and Computer Engineering The Ohio State University 2013 Master’s Examination Committee: Dr. Kun Huang, Advisor Dr. Raghu Machiraju Dr. Yuejie Chi ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Copyright by Jinchao Di 2013 ! ! Abstract Identifying and analyzing gene modules is important since it can help understand gene function globally and reveal the underlying molecular mechanism. In this thesis, we propose a method combining local graph sparsification and a gene similarity measurement method TOM. This method can detect gene modules from a weighted gene co-expression network more e↵ectively since we set a local threshold which can detect clusters with di↵erent densities. In our algorithm, we only retain one edge for each gene, which can generate more balanced gene clusters. To estimate the e↵ectiveness of our algorithm we use DAVID to functionally evaluate the gene list for each module we detect and compare our results with some well known algorithms. The result of our algorithm shows better biological relevance than the compared methods and the number of the meaningful biological clusters is much larger than other methods, implying we discover some previously missed gene clusters. Moreover, we carry out a robustness test by adding Gaussian noise with di↵erent variance to the expression data. We find that our algorithm is robust to noise. We also find that some hub genes considered as important genes could be artifacts.