TEDDY Fall 2016

Talk presented at the TEDDY Fall 2016 meeting on 11/8/16 in Washington DC.

Transcript

1. TEDDY Genetics Committee Meeting November 8, 2016 Charles R. Farber, Ph.D. Associate Professor, Center for Public Health Genomics, University of Virginia
2. Systems Genetics
3. Networks Disease Risk Genetic and Environmental inputs Genetic and environmental inputs are assimilated and transmitted through cellular networks
4. Networks Genetic and Environmental inputs Reconstructing networks in normal and diseased states can be used to identify what goes wrong in disease Normal T1D
5. Co-expression networks provide a way to view and quantify systems-level changes in disease relevant cell- types and tissues Samples Expression Weighted Gene Co-expression Network Analysis Zhang and Horvath, 2005. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 4, Article17.
6. Co-Expression Network Cell Cycle P=4.0 x 10-30 Mitochondria P=1.1 x 10-64 Extracellular Matrix P=1.9 x 10-16 Extracellular Matrix P=4.4 x 10-20 Ribosome P=5.1 x 10-14
7. Co-expression networks are like fly boxes
8. OVX vs. SHAM FDR Module 23 Kme 0.0 0.2 0.4 0.6 0.8 1.0 0.3 0.4 0.5 0.6 0.7 0.8 0.9 Snca r=-0.80, P=4.3 x 10-31 Snca-/- Snca+/+ OVX SHAM OVX SHAM 0 0.1 0.2 0.3 0.4 BV (mm3) P Geno = 0.21 P Surg = 3.1 x 10-3 P Int = 0.11 -6.0% -25.3% Module Connectivity Hub genes have been shown to be important in mediating module behavior OVX OVX SHAM SHAM Snca-/- Snca+/+ Module 17 Module 23
9. How can you use networks? • Associate module behavior with disease • Quantify network changes between cases and controls • Quantify network changes in disease over time • Integrate with other -omics and clinical data • Inform GWAS
10. Module Trait relationship tp 1 −1 −0.5 0 0.5 1 sex t1d persist_conf_gad persist_conf_ia2a persist_conf_m iaa persist_conf_ab t1d_diag_age persist_conf_age pos_diag_diff hla_category m iaaz ia2az rs2476601_A rs2816316_C rs11711054_G rs10517086_A rs4948088_A rs1004446_A rs7111341_A rs2292239_A rs3184504_A rs3825932_A rs12708716_G MEblack MEmidnightblue MElightgreen MEwhite MEbrown MEdarkred Edarkturquoise MEturquoise MEdarkgreen MEsalmon MEroyalblue MEsteelblue MEorange MEgrey60 MElightyellow MEmagenta MEdarkgrey MEgreen MEsaddlebrown MEcyan MEgreenyellow MEtan MEblue MEyellow MEdarkorange MEskyblue MEred MEpink MElightcyan MEpurple MEgrey −0.081 (0.3) 0.075 (0.3) 0.13 (0.2) −0.032 (0.8) −0.05 (0.6) 0.057 (0.4) 0.39 (0.02) 0.051 (0.6) 0.23 (0.2) −0.0017 (1) 0.054 (0.6) −0.014 (0.9) 0.059 (0.4) 0.019 (0.8) −0.075 (0.3) −0.14 (0.06) 0.048 (0.5) −0.051 (0.5) 0.018 (0.8) 0.13 (0.08) −0.074 (0.3) 0.0058 (0.9) 0.09 (0.2) 0.014 (0.9) 0.065 (0.4) 0.14 (0.2) 0.061 (0.6) −0.087 (0.4) −0.041 (0.6) 0.42 (0.01) 0.082 (0.4) 0.37 (0.06) −0.031 (0.7) 0.034 (0.8) 0.18 (0.08) 0.00044 (1) 0.08 (0.3) −0.1 (0.2) −0.11 (0.2) −0.048 (0.5) −0.047 (0.5) 0.063 (0.4) 0.02 (0.8) −0.08 (0.3) −0.035 (0.6) 0.04 (0.6) −0.0038 (1) −0.044 (0.5) 0.02 (0.8) 0.022 (0.8) −0.11 (0.3) 0.034 (0.6) 0.008 (1) 0.31 (0.003) −0.13 (0.5) 0.12 (0.09) −0.15 (0.2) −0.076 (0.5) 0.0051 (0.9) −0.12 (0.1) 0.13 (0.07) 0.01 (0.9) −0.015 (0.8) 0.16 (0.04) −0.034 (0.6) 0.088 (0.2) −0.0053 (0.9) −0.052 (0.5) −0.018 (0.8) 0.066 (0.4) −0.085 (0.2) 0.036 (0.7) 0.065 (0.5) −0.095 (0.4) 0.042 (0.6) 0.067 (0.7) 0.24 (0.02) 0.03 (0.9) 0.0024 (1) −0.14 (0.2) 0.014 (0.9) −0.011 (0.9) −0.046 (0.5) −0.042 (0.6) 0.015 (0.8) −0.16 (0.03) 0.12 (0.1) 0.016 (0.8) 0.045 (0.5) 0.05 (0.5) −0.065 (0.4) −0.06 (0.4) 0.013 (0.9) 0.046 (0.5) 0.035 (0.7) −0.014 (0.9) −0.047 (0.6) 0.058 (0.4) −0.032 (0.9) 0.19 (0.07) −0.13 (0.5) 0.011 (0.9) −0.016 (0.9) 0.016 (0.9) −0.057 (0.5) 0.026 (0.7) −0.16 (0.04) −0.0037 (1) −0.15 (0.04) 0.047 (0.5) 0.053 (0.5) 0.11 (0.1) −0.04 (0.6) −0.052 (0.5) −0.033 (0.7) −0.0086 (0.9) 0.024 (0.7) 0.11 (0.3) −0.047 (0.6) −0.16 (0.1) 0.1 (0.2) 0.14 (0.4) 0.33 (0.002) −0.0073 (1) 0.0022 (1) −0.11 (0.3) 0.019 (0.9) −0.036 (0.6) −0.043 (0.6) −0.039 (0.6) 0.04 (0.6) −0.11 (0.2) 0.099 (0.2) 0.075 (0.3) 0.11 (0.1) 0.012 (0.9) −0.14 (0.06) −0.045 (0.6) 0.049 (0.5) −0.049 (0.5) 0.034 (0.7) 0.12 (0.2) −0.06 (0.6) −0.13 (0.08) 0.057 (0.7) −0.029 (0.8) 0.22 (0.3) −0.072 (0.3) −0.088 (0.4) 0.36 (6e−04) −0.074 (0.3) 0.038 (0.6) 0.037 (0.6) 0.018 (0.8) −0.074 (0.3) 0.04 (0.6) 0.0084 (0.9) −0.12 (0.1) −0.087 (0.2) −0.077 (0.3) −0.0059 (0.9) 0.13 (0.07) −0.011 (0.9) −0.042 (0.7) 0.072 (0.5) −0.034 (0.7) −0.1 (0.2) −0.2 (0.2) −0.053 (0.6) −0.095 (0.6) −0.057 (0.4) −0.11 (0.3) 0.15 (0.2) −0.017 (0.8) 0.023 (0.8) 0.015 (0.8) 0.071 (0.3) −0.082 (0.3) 0.14 (0.07) −0.042 (0.6) −0.032 (0.7) −0.036 (0.6) −0.058 (0.4) −0.022 (0.8) 0.081 (0.3) −0.16 (0.03) −0.099 (0.3) 0.11 (0.3) 0.042 (0.7) −0.061 (0.4) −0.18 (0.3) −0.097 (0.4) −0.017 (0.9) −0.026 (0.7) −0.072 (0.5) 0.15 (0.2) −0.074 (0.3) −0.055 (0.5) 0.13 (0.07) 0.017 (0.8) −0.047 (0.5) 0.036 (0.6) −0.041 (0.6) −0.19 (0.01) 0.058 (0.4) 0.062 (0.4) −0.047 (0.5) 0.064 (0.4) −0.14 (0.05) −0.052 (0.6) −0.047 (0.6) −0.033 (0.7) −0.019 (0.8) 0.16 (0.4) 0.11 (0.3) 0.43 (0.02) −0.057 (0.4) −0.16 (0.1) 0.096 (0.4) −0.053 (0.5) 0.02 (0.8) 0.028 (0.7) 0.07 (0.3) −0.052 (0.5) 0.048 (0.5) −0.049 (0.5) −0.047 (0.5) 0.066 (0.4) −0.023 (0.8) −0.056 (0.5) 0.13 (0.08) 0.1 (0.2) 0.032 (0.8) 0.0087 (0.9) −0.024 (0.8) 0.097 (0.2) 0.14 (0.4) 0.062 (0.6) 0.097 (0.6) 0.078 (0.3) −0.07 (0.5) 0.08 (0.5) −0.12 (0.1) 0.15 (0.05) −0.056 (0.5) −0.033 (0.7) −0.048 (0.5) 0.048 (0.5) 0.11 (0.1) 0.097 (0.2) 0.047 (0.5) −0.15 (0.04) −0.1 (0.2) 0.14 (0.06) 0.018 (0.8) −0.021 (0.8) 0.096 (0.3) −0.08 (0.4) −0.03 (0.7) −0.14 (0.4) −0.077 (0.5) 0.034 (0.9) 0.0038 (1) −0.073 (0.5) 0.15 (0.2) −0.11 (0.1) 0.13 (0.08) −0.0087 (0.9) 0.052 (0.5) −0.048 (0.5) 0.1 (0.2) 0.053 (0.5) −0.013 (0.9) 0.0063 (0.9) −0.1 (0.2) −0.16 (0.04) −0.059 (0.4) 0.039 (0.6) −0.036 (0.7) 0.094 (0.4) 0.11 (0.3) 0.11 (0.1) 0.22 (0.2) −0.099 (0.4) 0.26 (0.2) 0.069 (0.3) −0.012 (0.9) 0.11 (0.3) −0.057 (0.4) 0.049 (0.5) −0.052 (0.5) −0.056 (0.5) 0.0051 (0.9) 0.027 (0.7) 0.0036 (1) 0.062 (0.4) 0.041 (0.6) 0.0031 (1) −0.037 (0.6) 0.017 (0.8) 0.037 (0.6) −0.01 (0.9) 0.031 (0.8) 0.068 (0.5) 0.12 (0.1) 0.045 (0.8) 0.014 (0.9) −0.056 (0.8) 0.076 (0.3) 0.033 (0.8) 0.015 (0.9) −0.068 (0.4) 0.11 (0.2) −0.13 (0.08) −0.045 (0.5) −0.097 (0.2) −0.089 (0.2) 0.1 (0.2) −0.026 (0.7) 0.082 (0.3) −0.049 (0.5) −0.071 (0.3) 0.068 (0.4) 0.02 (0.8) −0.026 (0.8) 0.052 (0.6) 0.034 (0.7) 0.064 (0.4) 0.059 (0.7) 0.023 (0.8) 0.076 (0.7) 0.041 (0.6) −0.031 (0.8) 0.18 (0.1) −0.11 (0.1) 0.16 (0.04) −0.13 (0.08) 0.027 (0.7) −0.18 (0.02) 0.016 (0.8) 0.09 (0.2) −0.027 (0.7) 0.036 (0.6) −0.11 (0.1) −0.14 (0.06) 0.093 (0.2) 0.081 (0.3) −0.12 (0.2) −0.23 (0.02) −0.11 (0.3) 0.031 (0.7) −0.013 (0.9) −0.0069 (0.9) −0.071 (0.7) 0.087 (0.2) 0.035 (0.7) −0.12 (0.3) 0.015 (0.8) −0.079 (0.3) 0.2 (0.006) 0.018 (0.8) 0.03 (0.7) −0.07 (0.4) 0.037 (0.6) 0.0019 (1) 0.026 (0.7) −0.079 (0.3) −0.027 (0.7) 0.063 (0.4) 0.12 (0.1) −0.024 (0.8) −0.083 (0.4) −0.038 (0.7) −0.052 (0.5) −0.5 (0.002) −0.11 (0.3) −0.47 (0.01) 0.077 (0.3) −0.015 (0.9) −0.1 (0.3) −0.024 (0.8) −0.092 (0.2) 0.13 (0.08) 0.12 (0.1) 0.055 (0.5) 0.12 (0.1) −0.041 (0.6) −0.012 (0.9) −0.046 (0.5) −0.053 (0.5) 0.005 (0.9) −0.035 (0.6) 0.068 (0.4) −0.038 (0.7) −0.16 (0.1) 0.06 (0.6) 0.011 (0.9) −0.29 (0.09) −0.077 (0.5) −0.22 (0.3) 0.079 (0.3) 0.057 (0.6) −0.21 (0.05) 0.046 (0.5) −0.11 (0.1) 0.12 (0.1) 0.053 (0.5) 0.23 (0.002) −0.054 (0.5) −0.0074 (0.9) −0.013 (0.9) 0.011 (0.9) 0.046 (0.5) 0.085 (0.3) −0.011 (0.9) 0.082 (0.3) 0.086 (0.4) 0.089 (0.4) 0.021 (0.8) 0.004 (1) 0.036 (0.8) −0.14 (0.2) 0.0016 (1) 0.069 (0.3) 0.051 (0.6) −0.04 (0.7) −0.063 (0.4) 0.057 (0.4) 0.12 (0.1) −0.065 (0.4) 0.2 (0.006) −0.042 (0.6) −0.0016 (1) 0.053 (0.5) −0.035 (0.6) −0.044 (0.6) −0.013 (0.9) 0.053 (0.5) −0.09 (0.2) −0.28 (0.005) −0.21 (0.04) 0.078 (0.4) 0.1 (0.2) 0.0084 (1) 0.062 (0.6) −0.003 (1) −0.099 (0.2) −0.11 (0.3) −0.21 (0.05) −0.056 (0.5) −0.014 (0.8) −0.088 (0.2) 0.019 (0.8) 0.0022 (1) −0.048 (0.5) −0.11 (0.1) −0.017 (0.8) 0.036 (0.6) 0.12 (0.1) −0.051 (0.5) −0.073 (0.3) −0.11 (0.1) 0.031 (0.8) −0.11 (0.3) −0.039 (0.7) 0.083 (0.3) 0.42 (0.01) 0.17 (0.1) 0.46 (0.01) 0.00038 (1) −0.11 (0.3) −0.048 (0.7) −0.0044 (1) 0.066 (0.4) −0.00075 (1) −0.018 (0.8) 0.045 (0.5) −0.067 (0.4) −0.012 (0.9) 0.078 (0.3) 0.081 (0.3) 0.00035 (1) 0.00061 (1) −0.06 (0.4) −0.15 (0.04) −0.039 (0.7) −0.053 (0.6) 0.057 (0.6) 0.084 (0.3) 0.084 (0.6) 0.03 (0.8) 0.13 (0.5) 0.029 (0.7) −0.038 (0.7) −0.14 (0.2) −0.0046 (1) −0.026 (0.7) 0.052 (0.5) −0.0075 (0.9) 0.054 (0.5) −0.071 (0.3) −0.018 (0.8) −0.022 (0.8) 0.15 (0.05) 0.075 (0.3) −0.011 (0.9) −0.098 (0.2) 0.0028 (1) 0.019 (0.8) 0.021 (0.8) 0.049 (0.6) 0.036 (0.6) 0.016 (0.9) −0.14 (0.2) −0.0069 (1) 0.041 (0.6) 0.1 (0.3) −0.18 (0.09) 0.066 (0.4) −0.061 (0.4) 0.018 (0.8) −0.085 (0.3) 0.11 (0.1) −0.065 (0.4) −0.0098 (0.9) 0.016 (0.8) 0.019 (0.8) 0.086 (0.3) 0.076 (0.3) 0.019 (0.8) −0.11 (0.1) −0.064 (0.5) 0.094 (0.4) 0.095 (0.3) 0.025 (0.7) −0.19 (0.3) −0.12 (0.2) −0.17 (0.4) 0.038 (0.6) 0.027 (0.8) −0.07 (0.5) −0.003 (1) −0.076 (0.3) 0.086 (0.3) −0.013 (0.9) 0.014 (0.8) −0.027 (0.7) −0.016 (0.8) −0.12 (0.1) 0.1 (0.2) 0.097 (0.2) −0.014 (0.8) 0.019 (0.8) −0.023 (0.8) −0.048 (0.6) −0.16 (0.1) −0.026 (0.8) −0.11 (0.1) −0.048 (0.8) 0.24 (0.02) 0.14 (0.5) 0.044 (0.5) 0.084 (0.4) −0.057 (0.6) −0.014 (0.9) −0.064 (0.4) −0.0017 (1) 0.034 (0.7) 0.011 (0.9) −0.23 (0.002) −0.11 (0.2) −0.18 (0.02) −0.064 (0.4) 0.11 (0.2) 0.025 (0.7) −0.016 (0.8) −0.033 (0.7) −0.11 (0.3) −0.1 (0.3) 0.15 (0.1) −0.028 (0.7) −0.04 (0.8) −0.14 (0.2) −0.14 (0.5) −0.12 (0.1) −0.037 (0.7) −0.11 (0.3) 0.017 (0.8) −0.048 (0.5) −0.042 (0.6) −0.097 (0.2) 0.019 (0.8) −0.068 (0.4) 0.021 (0.8) −0.017 (0.8) −0.18 (0.02) 0.1 (0.2) 0.033 (0.7) −0.14 (0.05) 0.029 (0.7) −0.091 (0.4) 0.09 (0.4) 0.11 (0.3) −0.068 (0.4) −0.088 (0.6) −0.18 (0.09) −0.079 (0.7) 0.062 (0.4) 0.23 (0.03) −0.022 (0.8) 0.06 (0.4) −0.068 (0.4) −0.15 (0.04) 0.015 (0.8) −0.11 (0.1) −0.068 (0.4) −0.078 (0.3) 0.024 (0.7) −0.17 (0.02) 0.092 (0.2) 0.023 (0.8) −0.072 (0.3) 0.023 (0.8) 0.093 (0.4) 0.033 (0.7) 0.032 (0.8) −0.072 (0.3) 0.032 (0.9) −0.043 (0.7) 0.19 (0.3) −0.06 (0.4) 0.14 (0.2) 0.11 (0.3) −0.043 (0.6) 0.096 (0.2) −0.0011 (1) 0.084 (0.3) 0.043 (0.6) −0.15 (0.05) 0.092 (0.2) −0.13 (0.07) −0.052 (0.5) 0.05 (0.5) −0.052 (0.5) −0.1 (0.2) −0.017 (0.8) −0.042 (0.7) 0.074 (0.5) 0.051 (0.6) −0.02 (0.8) 0.051 (0.8) −0.06 (0.6) −0.085 (0.7) −0.014 (0.8) 0.058 (0.6) −0.0025 (1) −0.0051 (0.9) 0.034 (0.6) 0.041 (0.6) 0.016 (0.8) 0.025 (0.7) −0.047 (0.5) 0.023 (0.8) −0.06 (0.4) 0.029 (0.7) 0.023 (0.8) −0.018 (0.8) −0.079 (0.3) 0.092 (0.2) 0.00011 (1) 0.031 (0.8) −0.034 (0.7) −0.048 (0.5) 0.27 (0.1) 0.034 (0.7) 0.031 (0.9) −0.026 (0.7) 0.042 (0.7) 0.081 (0.4) 0.015 (0.8) 0.12 (0.1) −0.027 (0.7) 0.025 (0.7) −0.027 (0.7) 0.0031 (1) 0.041 (0.6) 0.03 (0.7) −0.049 (0.5) −0.08 (0.3) −0.0011 (1) 7e−04 (1) 0.027 (0.7) 0.083 (0.4) −0.00096 (1) −0.1 (0.3) 0.072 (0.3) 0.032 (0.9) 0.24 (0.02) −0.066 (0.7) 0.012 (0.9) −0.043 (0.7) 0.014 (0.9) −0.04 (0.6) 0.01 (0.9) −0.13 (0.08) 0.0071 (0.9) −0.15 (0.04) 0.086 (0.3) 0.046 (0.5) 0.14 (0.06) −0.046 (0.5) −0.087 (0.2) −0.038 (0.6) Co-expression module-trait associations Ingrid Braenne, Ph.D. Senior Scientist
11. Module Trait relationship tp 1 sex t1d persist_conf_gad persist_conf_ia2a persist_conf_m iaa persist_conf_ab t1d_diag_age persist_conf_age pos_diag_diff hla_category m iaaz ia2az rs2476601_A rs2816316_C rs11711054_G rs10517086_A rs k e n e n d e e n n e e e 0 w a ey n n n w n e w e e d k n e ey −0.081 (0.3) 0.075 (0.3) 0.13 (0.2) −0.032 (0.8) −0.05 (0.6) 0.057 (0.4) 0.39 (0.02) 0.051 (0.6) 0.23 (0.2) −0.0017 (1) 0.054 (0.6) −0.014 (0.9) 0.059 (0.4) 0.019 (0.8) −0.075 (0.3) −0.14 (0.06) 0.014 (0.9) 0.065 (0.4) 0.14 (0.2) 0.061 (0.6) −0.087 (0.4) −0.041 (0.6) 0.42 (0.01) 0.082 (0.4) 0.37 (0.06) −0.031 (0.7) 0.034 (0.8) 0.18 (0.08) 0.00044 (1) 0.08 (0.3) −0.1 (0.2) −0.11 (0.2) −0.0038 (1) −0.044 (0.5) 0.02 (0.8) 0.022 (0.8) −0.11 (0.3) 0.034 (0.6) 0.008 (1) 0.31 (0.003) −0.13 (0.5) 0.12 (0.09) −0.15 (0.2) −0.076 (0.5) 0.0051 (0.9) −0.12 (0.1) 0.13 (0.07) 0.01 (0.9) 0.066 (0.4) −0.085 (0.2) 0.036 (0.7) 0.065 (0.5) −0.095 (0.4) 0.042 (0.6) 0.067 (0.7) 0.24 (0.02) 0.03 (0.9) 0.0024 (1) −0.14 (0.2) 0.014 (0.9) −0.011 (0.9) −0.046 (0.5) −0.042 (0.6) 0.015 (0.8) 0.013 (0.9) 0.046 (0.5) 0.035 (0.7) −0.014 (0.9) −0.047 (0.6) 0.058 (0.4) −0.032 (0.9) 0.19 (0.07) −0.13 (0.5) 0.011 (0.9) −0.016 (0.9) 0.016 (0.9) −0.057 (0.5) 0.026 (0.7) −0.16 (0.04) −0.003 (1) −0.0086 (0.9) 0.024 (0.7) 0.11 (0.3) −0.047 (0.6) −0.16 (0.1) 0.1 (0.2) 0.14 (0.4) 0.33 (0.002) −0.0073 (1) 0.0022 (1) −0.11 (0.3) 0.019 (0.9) −0.036 (0.6) −0.043 (0.6) −0.039 (0.6) 0.04 (0.6) 0.049 (0.5) −0.049 (0.5) 0.034 (0.7) 0.12 (0.2) −0.06 (0.6) −0.13 (0.08) 0.057 (0.7) −0.029 (0.8) 0.22 (0.3) −0.072 (0.3) −0.088 (0.4) 0.36 (6e−04) −0.074 (0.3) 0.038 (0.6) 0.037 (0.6) 0.018 (0.8) 0.13 (0.07) −0.011 (0.9) −0.042 (0.7) 0.072 (0.5) −0.034 (0.7) −0.1 (0.2) −0.2 (0.2) −0.053 (0.6) −0.095 (0.6) −0.057 (0.4) −0.11 (0.3) 0.15 (0.2) −0.017 (0.8) 0.023 (0.8) 0.015 (0.8) 0.071 (0.3) 0.081 (0.3) −0.16 (0.03) −0.099 (0.3) 0.11 (0.3) 0.042 (0.7) −0.061 (0.4) −0.18 (0.3) −0.097 (0.4) −0.017 (0.9) −0.026 (0.7) −0.072 (0.5) 0.15 (0.2) −0.074 (0.3) −0.055 (0.5) 0.13 (0.07) 0.017 (0.8) 0.064 (0.4) −0.14 (0.05) −0.052 (0.6) −0.047 (0.6) −0.033 (0.7) −0.019 (0.8) 0.16 (0.4) 0.11 (0.3) 0.43 (0.02) −0.057 (0.4) −0.16 (0.1) 0.096 (0.4) −0.053 (0.5) 0.02 (0.8) 0.028 (0.7) 0.07 (0.3) 0.13 (0.08) 0.1 (0.2) 0.032 (0.8) 0.0087 (0.9) −0.024 (0.8) 0.097 (0.2) 0.14 (0.4) 0.062 (0.6) 0.097 (0.6) 0.078 (0.3) −0.07 (0.5) 0.08 (0.5) −0.12 (0.1) 0.15 (0.05) −0.056 (0.5) −0.03 (0.7) 0.14 (0.06) 0.018 (0.8) −0.021 (0.8) 0.096 (0.3) −0.08 (0.4) −0.03 (0.7) −0.14 (0.4) −0.077 (0.5) 0.034 (0.9) 0.0038 (1) −0.073 (0.5) 0.15 (0.2) −0.11 (0.1) 0.13 (0.08) −0.0087 (0.9) 0.052 (0.5) −0.059 (0.4) 0.039 (0.6) −0.036 (0.7) 0.094 (0.4) 0.11 (0.3) 0.11 (0.1) 0.22 (0.2) −0.099 (0.4) 0.26 (0.2) 0.069 (0.3) −0.012 (0.9) 0.11 (0.3) −0.057 (0.4) 0.049 (0.5) −0.052 (0.5) −0.05 (0.5) 0.017 (0.8) 0.037 (0.6) −0.01 (0.9) 0.031 (0.8) 0.068 (0.5) 0.12 (0.1) 0.045 (0.8) 0.014 (0.9) −0.056 (0.8) 0.076 (0.3) 0.033 (0.8) 0.015 (0.9) −0.068 (0.4) 0.11 (0.2) −0.13 (0.08) −0.04 (0.5) 0.068 (0.4) 0.02 (0.8) −0.026 (0.8) 0.052 (0.6) 0.034 (0.7) 0.064 (0.4) 0.059 (0.7) 0.023 (0.8) 0.076 (0.7) 0.041 (0.6) −0.031 (0.8) 0.18 (0.1) −0.11 (0.1) 0.16 (0.04) −0.13 (0.08) 0.027 (0.7) 0.093 (0.2) 0.081 (0.3) −0.12 (0.2) −0.23 (0.02) −0.11 (0.3) 0.031 (0.7) −0.013 (0.9) −0.0069 (0.9) −0.071 (0.7) 0.087 (0.2) 0.035 (0.7) −0.12 (0.3) 0.015 (0.8) −0.079 (0.3) 0.2 (0.006) 0.018 (0.8) 0.063 (0.4) 0.12 (0.1) −0.024 (0.8) −0.083 (0.4) −0.038 (0.7) −0.052 (0.5) −0.5 (0.002) −0.11 (0.3) −0.47 (0.01) 0.077 (0.3) −0.015 (0.9) −0.1 (0.3) −0.024 (0.8) −0.092 (0.2) 0.13 (0.08) 0.12 (0.1) −0.035 (0.6) 0.068 (0.4) −0.038 (0.7) −0.16 (0.1) 0.06 (0.6) 0.011 (0.9) −0.29 (0.09) −0.077 (0.5) −0.22 (0.3) 0.079 (0.3) 0.057 (0.6) −0.21 (0.05) 0.046 (0.5) −0.11 (0.1) 0.12 (0.1) 0.053 (0.5) −0.011 (0.9) 0.082 (0.3) 0.086 (0.4) 0.089 (0.4) 0.021 (0.8) 0.004 (1) 0.036 (0.8) −0.14 (0.2) 0.0016 (1) 0.069 (0.3) 0.051 (0.6) −0.04 (0.7) −0.063 (0.4) 0.057 (0.4) 0.12 (0.1) −0.06 (0.4) 0.053 (0.5) −0.09 (0.2) −0.28 (0.005) −0.21 (0.04) 0.078 (0.4) 0.1 (0.2) 0.0084 (1) 0.062 (0.6) −0.003 (1) −0.099 (0.2) −0.11 (0.3) −0.21 (0.05) −0.056 (0.5) −0.014 (0.8) −0.088 (0.2) 0.019 (0.8) −0.073 (0.3) −0.11 (0.1) 0.031 (0.8) −0.11 (0.3) −0.039 (0.7) 0.083 (0.3) 0.42 (0.01) 0.17 (0.1) 0.46 (0.01) 0.00038 (1) −0.11 (0.3) −0.048 (0.7) −0.0044 (1) 0.066 (0.4) −0.00075 (1) −0.01 (0.8) −0.06 (0.4) −0.15 (0.04) −0.039 (0.7) −0.053 (0.6) 0.057 (0.6) 0.084 (0.3) 0.084 (0.6) 0.03 (0.8) 0.13 (0.5) 0.029 (0.7) −0.038 (0.7) −0.14 (0.2) −0.0046 (1) −0.026 (0.7) 0.052 (0.5) −0.007 (0.9) −0.098 (0.2) 0.0028 (1) 0.019 (0.8) 0.021 (0.8) 0.049 (0.6) 0.036 (0.6) 0.016 (0.9) −0.14 (0.2) −0.0069 (1) 0.041 (0.6) 0.1 (0.3) −0.18 (0.09) 0.066 (0.4) −0.061 (0.4) 0.018 (0.8) −0.08 (0.3) 0.019 (0.8) −0.11 (0.1) −0.064 (0.5) 0.094 (0.4) 0.095 (0.3) 0.025 (0.7) −0.19 (0.3) −0.12 (0.2) −0.17 (0.4) 0.038 (0.6) 0.027 (0.8) −0.07 (0.5) −0.003 (1) −0.076 (0.3) 0.086 (0.3) −0.01 (0.9) 0.019 (0.8) −0.023 (0.8) −0.048 (0.6) −0.16 (0.1) −0.026 (0.8) −0.11 (0.1) −0.048 (0.8) 0.24 (0.02) 0.14 (0.5) 0.044 (0.5) 0.084 (0.4) −0.057 (0.6) −0.014 (0.9) −0.064 (0.4) −0.0017 (1) 0.034 (0.7) −0.016 (0.8) −0.033 (0.7) −0.11 (0.3) −0.1 (0.3) 0.15 (0.1) −0.028 (0.7) −0.04 (0.8) −0.14 (0.2) −0.14 (0.5) −0.12 (0.1) −0.037 (0.7) −0.11 (0.3) 0.017 (0.8) −0.048 (0.5) −0.042 (0.6) −0.09 (0.2) −0.14 (0.05) 0.029 (0.7) −0.091 (0.4) 0.09 (0.4) 0.11 (0.3) −0.068 (0.4) −0.088 (0.6) −0.18 (0.09) −0.079 (0.7) 0.062 (0.4) 0.23 (0.03) −0.022 (0.8) 0.06 (0.4) −0.068 (0.4) −0.15 (0.04) 0.015 (0.8) −0.072 (0.3) 0.023 (0.8) 0.093 (0.4) 0.033 (0.7) 0.032 (0.8) −0.072 (0.3) 0.032 (0.9) −0.043 (0.7) 0.19 (0.3) −0.06 (0.4) 0.14 (0.2) 0.11 (0.3) −0.043 (0.6) 0.096 (0.2) −0.0011 (1) 0.084 (0.3) −0.1 (0.2) −0.017 (0.8) −0.042 (0.7) 0.074 (0.5) 0.051 (0.6) −0.02 (0.8) 0.051 (0.8) −0.06 (0.6) −0.085 (0.7) −0.014 (0.8) 0.058 (0.6) −0.0025 (1) −0.0051 (0.9) 0.034 (0.6) 0.041 (0.6) 0.016 (0.8) −0.079 (0.3) 0.092 (0.2) 0.00011 (1) 0.031 (0.8) −0.034 (0.7) −0.048 (0.5) 0.27 (0.1) 0.034 (0.7) 0.031 (0.9) −0.026 (0.7) 0.042 (0.7) 0.081 (0.4) 0.015 (0.8) 0.12 (0.1) −0.027 (0.7) 0.025 (0.7) 7e−04 (1) 0.027 (0.7) 0.083 (0.4) −0.00096 (1) −0.1 (0.3) 0.072 (0.3) 0.032 (0.9) 0.24 (0.02) −0.066 (0.7) 0.012 (0.9) −0.043 (0.7) 0.014 (0.9) −0.04 (0.6) 0.01 (0.9) −0.13 (0.08) 0.0071 (0.9) • • • • • • • • • • • • • • • • • • • • • • • • • • • −0.1 0.0 0.1 0.2 0 200 400 600 800 1200 cor=0.46, p=0.016 module greenyellow days between persistent confirmed and t1d age • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • −0.1 0.0 0.1 0.2 0 500 1000 1500 2000 cor=0.33, p=0.0015 module darkred persistent confirmed age
12. How can you use networks? • Associate module behavior with disease • Quantify network changes between cases and controls • Quantify network changes in disease over time • Integrate with other -omics and clinical data • Inform GWAS