HotNet Background Determine significantly mutated subnetworks in a - PowerPoint PPT Presentation

Jan 30, 2023 •619 likes •737 views

HotNet Background Determine significantly mutated subnetworks in a large gene interaction network Problems with current methods Frequency doesnt always predict significance Nave subnetwork analysis Enumeration prohibits

HotNet
Background • Determine significantly mutated subnetworks in a large gene interaction network • Problems with current methods – Frequency doesn’t always predict significance – Naïve subnetwork analysis • Enumeration prohibits subnetworks of reasonable size • Large number of hypotheses makes statistically significant difficult • Hub genes make for small gene diameters
HotNet Overview 1. Formulate an influence measure between pairs of genes in the network 2. Identify subnetworks with Combinatorial Model or Enhanced Influence Model 3. Two-stage multiple hypothesis test to mitigate testing of large number of hypotheses
Influence Graph • Identify subnetworks that are significant with respect to a set of mutated genes
Diffusion Amount of fluid @ node V at time T Amount of fluid at all nodes L is the laplacian matrix of the graph Dynamics of the continuous process • Interpret f i as the influence of gene g s on g i
Combinatorial Model • Takes in influence measure between genes to discover significant subnetworks
Enhanced Influence Model • Enhance the influence measure between genes by the number of mutations observed in each gene
Statistics sample and H 0 • Calibrates with H o gene – Sample: mutations placed at random nodes – Gene: Move genes around…..? • Compute significance of number of subnetworks • Bound FDR
Experimental Data

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