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Project2 Daotai Nie, PhD Hongwei Dong PhD Wenjun Zhang PhD

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1 Project2 Daotai Nie, PhD Hongwei Dong PhD Wenjun Zhang PhD
Ann Kirchmaier PhD Jixin Ding PhD Xiangqi Meng PhD

2 Total patients:119 Ctr: 70 NAFLD: 49

3 Results 190 genes (after removal of bottom 25% of low expression genes, performing logistic normalization, set FDR cutoff value to 0.05, run linear regression to identify the top genes with significant association with high fat level in liver tissue) Name GENE_SYMBOL FC beta_estimate pvalue adjusted_pvalue GAS6 2.62E-07 C9orf125 3.36E-07 1.26E-07 KDELR3 3.41E-07 IGHA1 4.93E-07 TSPYL5 6.20E-07 OLFM2 1.08E-06 RET 1.48E-06 1.89E-06 ARSF 1.78E-06 IGKC 3.60E-06 MAMDC4 3.21E-06 3.76E-06 FLJ30901 3.11E-06 3.96E-06

4 91 genes IPA Pathway Analysis (p=0
91 genes IPA Pathway Analysis (p=0.05) ready molecules across observations with p=0.001 to (110 mapped IDs, 80 unmapped IDs) for All Pathways Entrez Gene Name FDR Location Type(s) Biomarker Application(s) IGH immunoglobulin heavy locus 0.010 Other other diagnosis,prognosis IGHA1 immunoglobulin heavy constant alpha 1 0.014 Extracellular Space IGHG1 immunoglobulin heavy constant gamma 1 (G1m marker) 0.012 peptidase IGLL1/IGLL5 immunoglobulin lambda like polypeptide 1 0.006 Plasma Membrane

5 IPA Biomarker selection
Symbol Entrez Gene Name FDR Expected Location Type(s) Biomarker Application(s) CAMK1 calcium/calmodulin dependent protein kinase I 0.044 Up Cytoplasm kinase PLCB1 phospholipase C beta 1 0.042 enzyme PLCH2 phospholipase C eta 2 0.008 PRKCE protein kinase C epsilon 0.016 disease progression

6 Organ System + Hepatoma Overlapping Canonical Pathways
67 genes IPA Pathway Analysis (p=0.05) for Hepatoma Cell Line & Organ Systems

7 Tissue Development Pathway/Growth of Epithelial Tissues

8

9 ID Name GENE_SYMBOL FC beta_estimate pvalue adjusted_pvalue 3320 GAS6 2.62E-07 42396 C9orf125 1.26E-07 30877 3.36E-07 32794 OLFM2 1.08E-06 2654 RET 1.48E-06 21190 ARSF 1.78E-06 26093 C15orf52 4.59E-06 22960 SATB2 1.30E-05 11791 HPS5 1.08E-05 44682 DERL3 1.19E-05 10297 1.07E-05 5506 CNTN3 1.45E-05

10 Future Directions Validate, Validate, Validate in the independent Cohort Figure out what these genes do. Development of Assay system

11 Acknowledgements: The BigTAP Workshop Team Min Zhang, MD, PhD
Department of Statistics Wanqing Liu, PhD Department of Medicinal Chemistry and Molecular Pharmacology Purdue University Center for Cancer Research Peter Pascuzzi, PhD Purdue University Libraries James C. Fleet, PhD Department of Nutrition Science Doug Crabill, Ph.D Min Ren Department of Statistics Chen Chen


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