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lecture_14 - Human Regulatory Networks Lecture 14...

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Human Regulatory Networks Lecture 14 6.874J/7.90J/6.807 David Gifford
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(Q1) How can we explain complex experimental data with models?
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The Model Spectrum Detailed Fragile Coarse Robust Diagram removed for copyright reasons. Complex process chart.
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Alternative data representations Two diagrams removed for copyright reasons.
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Why graphical models? Handle imperfect data and imperfect theory robustly Biologically interpretable and familiar Permit arbitrary (more than pair-wise) interactions Produce results with statistical significance Remain methodologically principled Combinable for network reassembly
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(Q2) How can we judge the significance of models?
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Comparing alternative network structures Expression Data Expression, Location Data Normalization Normalization Model 1 Model Scoring Data-Driven Analysis Model N Data Display P (M1 | D) P (MN | D)
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We can easily compute P(D | S, θ ) C P(C=1|A=0,B=0) = 0.1 P(C=1|A=0,B=1) = 0.1 P(C=1|A=1,B=0) = 0.1 P(C=1|A=1,B=1) = 0.8 P(D=1|C=0) = 0.8 P(D=1|C=1) = 0.3 θ Parameters P(B=1) = 0.8 P(A=1) = 0.6 A D B
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How can we score models without parameters? P(S | D) P(D) = P(D | S) P(S) Likelihood term is computed as an average with a distribution over parameter settings θ : c S P S D P D S P + + = = ) ( log ) | ( log ) | ( log Score = θ θ θ d S P S D P S D P ) | ( ) , | ( ) | (
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Scores need to be interpreted properly Scores are not absolute, relative comparisons are needed May not have informative data to distinguish models Relevant variables may not be represented It’s just science… an iterative process
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Human Regulatory Pathways Human Biology The organism and its components Motivation: improved understanding of health and disease Gene Expression Regulatory Pathways Cell division cycle Tissue-specific gene expression programs Immune response Cell-cell signaling pathways • Development What are the big problems, key questions and challenges?
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Human Tissues Brain and Spinal Cord Cerebrum Cerebellum Ganglia & nerves Circulatory System Heart Vascular system Digestive System Esophagus Stomach Intestines Liver Pancreas Urinary System Kidney Urinary tract Respiratory System Airways Lungs Reproductive Organs Ovary Uterus Breast Testis Skeletal and Muscular Bone Muscle
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