Another obvious concern is that it can only evaluate the genetic contribution of genes known to act within pathways.
One obvious concern of the pathway approach is that it can only evaluate the genetic contribution of genes known to act within pathways.
Finally, a relatively smaller proportion of synthetic lethal interactions are within pathways that can sustain one, but not two, mutations without loss of function (Figure 1D).
Biologically, we expected the enrichment of physical interactions within pathways we identified, which was an important component in Kelley and Ideker [1] and Ulitsky and Shamir [8].
Its connectivity is characterized by segregated parallel pathways to and from cortex and by convergence, within pathways, of signals across many cortical areas [20], [21], [22].
More recently, gene interaction information has been introduced into the gene selection (GS) process to account for the known ability of genes to interact or react within pathways or common modules.
We observed downregulation of signaling components within pathways controlled by the Bone Morphogenic Proteins (BMPs) (Figure 5): BMPs are the largest group of proteins within the TGF-β superfamily, and they have been particularly implicated in eye development [47].
We therefore estimated the bias of the distribution of all such newly-reported SL interactions in favor of appearing between rather than within pathways (see the Methods section for computational details).
For the pathway analysis a stricter statistical cut-off was utilized (1% FDR), while presented pathways were colored by 1.5 FC and 5% FDR so that the robust trends within pathways could be visualized.
The identification of genes with known biological roles in heart valve formation (AXIN1 and ENG) and additionally within pathways and regulatory networks previously associated with BAV in family-based studies demonstrates the power of association testing that incorporates biological knowledge.
These results indicated that using more samples may conduct more reliable correlations within pathways.
