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Supporting Information Supporting information MACROSCALE CONNECTOME MANIFOLD EXPANSION IN ADOLESCENCE Bo-yong Parka, Richard A. I. Bethlehemb,c, Casey Paquolaa, Sara Larivièrea, Raul R. Crucesa, Reinder Vos de Waela, Neuroscience in Psychiatry Network (NSPN) Consortium2 , Edward T. Bullmorec, Boris C. Bernhardta aMcConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; bAutism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; cBrain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom Corresponding Authors: Boris C. Bernhardt, PhD Multimodal Imaging and Connectome Analysis Lab McConnell Brain Imaging Centre Montreal Neurological Institute and Hospital McGill University Montreal, Quebec, Canada Phone: +1-514-398-3579 Email: [email protected] Bo-yong Park, PhD Multimodal Imaging and Connectome Analysis Lab McConnell Brain Imaging Centre Montreal Neurological Institute and Hospital McGill University Montreal, Quebec, Canada Email: [email protected] 2A complete list of investigators from the Neuroscience in Psychiatry Network (NSPN) Consortium can be found in the Supporting Information. Fig. S1 | Modular structures. (A) Pipeline for constructing consistency matrix. We constructed individual subject-wise consistency matrix by considering whether two different nodes were involved in the same module. (B) Group-wise consistency matrix was constructed by averaging subject-wise consistency matrices. The k-means clustering with silhouette coefficient were used for defining modules. Seven modules on the brain surface are reported on the right side. Fig. S2 | Age-related trends in connectome topology measures. Age-related changes in manifold eccentricity, degree centrality, connectivity distance, within-module degree, and participation coefficient. Abbreviation: y, years. Fig. S3 | Association to morphological and microstructural effects. The t-statistics of the identified regions that showed significant age-related longitudinal changes in (A) cortical thickness and (B) MT. Stratification of age-related changes in cortical thickness and MT along cortical hierarchy 66 and functional community 67. Fig. S4 | Cognitive decoding of the selected regions for IQ prediction. (A) Probability of selected cortical and subcortical regions for predicting future IQ using both baseline and maturational changes (see Fig. 6). (B) A word cloud derived by cognitive decoding using NeuroSynth 74. Fig. S5 | Structural connectome manifolds using Schaefer 300 atlas. (A-D) Main findings replicated using a different parcellation scale. For details, see Fig. 1. Fig. S6 | Sensitivity analysis for site and sex. (A) The t-statistics of identified regions that showed significant age-related changes in manifold eccentricity in a longitudinal setting. (B) Pearson’s correlation between age and manifold eccentricity for each site and (C) biological sex. Fig. S7 | Structural connectome manifolds using different template dataset. (A-C) Structural connectome manifolds and association to age using different template cohort. Three representative cases are reported. For details, see Figure 1. Data S1 | Significant gene lists correlated with patterns of manifold eccentricity changes across age. Gene symbol with name and t-statistic as well as false discover rate (FDR) corrected p-value are reported in the Supplementary Data file (Supplementary_Data1.xlsx). Symbol Name t p-FDR CHST9 carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 9 -24.76 0.0058 SHD Src homology 2 domain containing transforming protein D 24.20 0.0058 SPTSSB serine palmitoyltransferase, small subunit B 20.90 0.0088 CPNE9 copine family member IX 20.12 0.0095 COL5A1 collagen, type V, alpha 1 18.34 0.0097 POLR2L polymerase (RNA) II (DNA directed) polypeptide L, 7.6kDa -18.46 0.0097 RSPO4 R-spondin 4 -18.57 0.0097 COX7A1 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) 17.57 0.0100 FAM20A family with sequence similarity 20, member A 17.77 0.0100 ITPR1 inositol 1,4,5-trisphosphate receptor, type 1 17.39 0.0100 HAPLN4 hyaluronan and proteoglycan link protein 4 16.59 0.0116 GLUD1 glutamate dehydrogenase 1 -16.27 0.0118 KCNN3 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3 -15.51 0.0118 PPL periplakin 15.24 0.0118 RELL2 RELT-like 2 16.34 0.0118 RGS7 regulator of G-protein signaling 7 15.24 0.0118 SMARCD3 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 -15.52 0.0118 PRSS16 protease, serine, 16 (thymus) 14.22 0.0132 SCN1A sodium channel, voltage-gated, type I, alpha subunit 14.23 0.0132 STX19 syntaxin 19 14.50 0.0132 NGB neuroglobin 13.77 0.0137 DDAH2 dimethylarginine dimethylaminohydrolase 2 -13.61 0.0141 GPD2 glycerol-3-phosphate dehydrogenase 2 (mitochondrial) -13.57 0.0141 EPN3 epsin 3 13.29 0.0146 LRRC38 leucine rich repeat containing 38 13.22 0.0146 FBLN7 fibulin 7 13.06 0.0150 MACROD2 MACRO domain containing 2 -13.01 0.0151 NKAIN4 Na+/K+ transporting ATPase interacting 4 -12.70 0.0160 CPLX1 complexin 1 12.48 0.0164 EXTL2 exostoses (multiple)-like 2 12.53 0.0164 FLRT3 fibronectin leucine rich transmembrane protein 3 12.48 0.0164 LYPD1 LY6/PLAUR domain containing 1 -12.38 0.0164 GLCCI1 glucocorticoid induced transcript 1 12.24 0.0165 LAG3 lymphocyte-activation gene 3 12.06 0.0168 DNAH14 dynein, axonemal, heavy chain 14 -11.32 0.0170 KCNAB3 potassium voltage-gated channel, shaker-related subfamily, beta member 3 11.95 0.0170 PREP prolyl endopeptidase 11.82 0.0170 SCN1B sodium channel, voltage-gated, type I, beta subunit 11.67 0.0170 SCRT1 scratch homolog 1, zinc finger protein (Drosophila) 11.53 0.0170 SHROOM3 shroom family member 3 11.40 0.0170 SPAG4 sperm associated antigen 4 11.30 0.0170 TDRD1 tudor domain containing 1 11.74 0.0170 TNNC2 troponin C type 2 (fast) 11.88 0.0170 TPK1 thiamin pyrophosphokinase 1 11.39 0.0170 FGF18 fibroblast growth factor 18 11.18 0.0172 KLHL13 kelch-like 13 (Drosophila) -11.16 0.0172 ASB13 ankyrin repeat and SOCS box containing 13 10.81 0.0173 LINC00473 long intergenic non-protein coding RNA 473 10.85 0.0173 MYO15A myosin XVA 11.01 0.0173 S100A10 S100 calcium binding protein A10 -10.92 0.0173 SIX4 SIX homeobox 4 10.79 0.0173 STAMBPL1 STAM binding protein-like 1 10.87 0.0173 STXBP5L syntaxin binding protein 5-like 10.97 0.0173 SLIT3 slit homolog 3 (Drosophila) -10.73 0.0177 GABRA1 gamma-aminobutyric acid (GABA) A receptor, alpha 1 10.66 0.0179 FES feline sarcoma oncogene 10.65 0.0179 MIR31HG MIR31 host gene (non-protein coding) 10.57 0.0181 OSBPL6 oxysterol binding protein-like 6 10.59 0.0181 GABRD gamma-aminobutyric acid (GABA) A receptor, delta 10.53 0.0182 SCAPER S-phase cyclin A-associated protein in the ER -10.46 0.0185 GNG4 guanine nucleotide binding protein (G protein), gamma 4 -10.38 0.0185 IL17RD interleukin 17 receptor D -10.37 0.0185 SRPK1 SRSF protein kinase 1 10.38 0.0185 EIF4E1B eukaryotic translation initiation factor 4E family member 1B 10.30 0.0187 MAP3K13 mitogen-activated protein kinase kinase kinase 13 10.30 0.0187 NTSR2 neurotensin receptor 2 -10.28 0.0187 CFD complement factor D (adipsin) -10.24 0.0188 UCHL3 ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) -10.20 0.0189 KCNA2 potassium voltage-gated channel, shaker-related subfamily, member 2 10.13 0.0191 PVALB parvalbumin 10.01 0.0195 UCHL5 ubiquitin carboxyl-terminal hydrolase L5 10.02 0.0195 HIVEP2 human immunodeficiency virus type I enhancer binding protein 2 9.90 0.0200 CADPS2 Ca++-dependent secretion activator 2 9.80 0.0202 CITED2 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 9.78 0.0202 GLS2 glutaminase 2 (liver, mitochondrial) 9.82 0.0202 STRBP spermatid perinuclear RNA binding protein 9.81 0.0202 PTPRA protein tyrosine phosphatase, receptor type, A -9.75 0.0202 CCNI cyclin I 9.39 0.0210 DERL1 derlin 1 -9.38 0.0210 EIF5A2 eukaryotic translation initiation factor 5A2 9.55 0.0210 KBTBD6 kelch repeat and BTB (POZ) domain containing 6 -9.46 0.0210 PDLIM5 PDZ and LIM domain 5 -9.41 0.0210 SLC39A14 solute carrier family 39 (zinc transporter), member 14 9.45 0.0210 SYCP2 synaptonemal complex protein 2 9.49 0.0210 TPTE2P6 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 6 9.57 0.0210 ZNF385B zinc finger protein 385B 9.49 0.0210 MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) 9.37 0.0210 ZBTB16 zinc finger and BTB domain containing 16 9.34 0.0210 KCNS1 potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1 9.28 0.0214 PLXDC1 plexin domain containing 1 9.24 0.0216 RAD54B RAD54 homolog B (S. cerevisiae) 9.23 0.0216 NAPEPLD N-acyl phosphatidylethanolamine phospholipase D 9.18 0.0219 HTR2C 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled -9.12 0.0220 NEFH neurofilament, heavy polypeptide 9.12 0.0220 BHMT2 betaine--homocysteine S-methyltransferase 2 -9.02 0.0222 ECM1 extracellular matrix protein 1 9.05 0.0222 PHYH phytanoyl-CoA 2-hydroxylase 9.03 0.0222 CCDC8 coiled-coil domain containing 8 -8.88 0.0223 CTNNAL1 catenin (cadherin-associated protein), alpha-like 1 8.87 0.0223 EPCAM epithelial cell adhesion molecule -8.84 0.0224 ANKH ankylosis, progressive homolog (mouse) 8.79 0.0225 LIX1 Lix1 homolog (chicken) -8.80 0.0225 ROBO1 roundabout, axon guidance receptor, homolog 1 (Drosophila) -8.82 0.0225 TMEM132E transmembrane protein 132E 8.79 0.0225 ST3GAL6 ST3 beta-galactoside alpha-2,3-sialyltransferase 6 8.75 0.0225 FNDC4 fibronectin type III domain
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