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Refining cellular pathway models using an ensemble of heterogeneous data sources


Type

Article

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Authors

Franks, AM 
Airoldi, EM 

Abstract

© Institute of Mathematical Statistics, 2018. Improving current models and hypotheses of cellular pathways is one of the major challenges of systems biology and functional genomics. There is a need for methods to build on established expert knowledge and reconcile it with results of new high-throughput studies. Moreover, the available sources of data are heterogeneous, and the data need to be integrated in different ways depending on which part of the pathway they are most informative for. In this paper, we introduce a compartment specific strategy to integrate edge, node and path data for refining a given network hypothesis. To carry out inference, we use a local-move Gibbs sampler for updating the pathway hypothesis from a compendium of heterogeneous data sources, and a new network regression idea for integrating protein attributes. We demonstrate the utility of this approach in a case study of the pheromone response MAPK pathway in the yeast S. cerevisiae.

Description

Keywords

Bayesian inference, Multi-level modeling, regulation and signaling dynamics, statistical network analysis

Journal Title

Annals of Applied Statistics

Conference Name

Journal ISSN

1932-6157
1941-7330

Volume Title

12

Publisher

Institute of Mathematical Statistics
Sponsorship
Cancer Research UK (C14303/A17197)
This work was supported, in part, by NIH grant R01 GM-096193, NSF CAREER grant IIS-1149662, and by MURI award W911NF-11-1-0036 to Harvard University. EMA is an Alfred P. Sloan Research Fellow and a Shutzer Fellow at the Radcliffe Institute for Advanced Studies. FM acknowledges support from the University of Cambridge, Cancer Research UK (C14303/A17197), and Hutchison Whampoa Limited. FM and EMA contributed equally to this work.