Volume 12 Supplement 11
Toward PWAS: discovering pathways associated with human disorders
© Guney and Oliva; licensee BioMed Central Ltd. 2011
Published: 21 November 2011
The past decade has witnessed dramatic advances in genome sequencing and a substantial shift in the number of genome wide association studies (GWAS). These efforts have expanded considerably our knowledge on the sequential variations in Human DNA and their consequences on the human biology. Nevertheless, complex genetic disorders often involve products of multiple genes acting cooperatively and pinpointing the decisive elements of such disease pathways remains a challenge. Network biology recently proved its use in identifying candidate disease genes based on the simple observation that proteins translated by phenotypically related genes tend to interact, the so called guilt-by-association principle.
Here, we present GUILD (Genes Underlying Inheritance Linked Disorders), a network-based candidate disease-gene prioritization framework which reveals the pathways associated with the disorder (pathway wide association study, PWAS). We exploit several distinct plausible communication mechanisms of known genes associated with the phenotype emerging from the topology of the interaction network. We used three sources of gene-phenotypic association to specify nodes involved in a disorder (seeds for the methods proposed): Online Mendelian Inheritance in Man (OMIM) database  and two published data sets (by Goh et al. , and Chen et al. ).
Results and discussion
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