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COMMUNITY OF LIVING MACHINES. "The properties of living cells are mediated by a huge number of ever-changing interactions of their component macromolecules forming living machines; collectively, these are termed the interactome. Pathogenic alterations in interactomes mechanistically underlie diseases." https://lnkd.in/eVepjNC View in LinkedIn

BEYOND VIEW. "These findings indicate that many local neighborhoods of the interactome represent the observable part of the true, larger and denser disease modules." http://science.sciencemag.org/content/347/6224/1257601 View in LinkedIn

GIANT TASK. "Even considering only one splice variant per gene, approximately 20,000 protein-coding genes must be handled and ∼200 million protein pairs tested to generate a comprehensive binary reference PPI map. Even with nearly complete, high-quality reference interactome maps of biophysical interactions, how can the biological relevance of each interaction be evaluated under physiological conditions?" (PPI = Protein-Protein Interactions). http://www.sciencedirect.com/science/article/pii/S0092867414014226 View in LinkedIn

DISEASE MODULES. "We find that disease proteins associated with 226 diseases are clustered in the same network neighborhood, displaying a statistically significant tendency to form identifiable disease modules. The higher the degree of agglomeration of the disease proteins within the interactome, the higher the biological and functional similarity of the corresponding genes." http://science.sciencemag.org/content/347/6224/1257601 View in LinkedIn

GENOME-PHENOTYPE LINKS. "Even when identified, it is often unclear how a causal mutation perturbs the function of the corresponding gene or gene product. To “connect the dots” of the genomic revolution, functions and context must be assigned to large numbers of genotypic changes." http://www.sciencedirect.com/science/article/pii/S0092867414014226 View in LinkedIn

DISEASE CLUSTER. "The documented propensity of disease-associated proteins to interact with each other suggests that they tend to cluster in the same neighborhood of the interactome, forming a disease module, a connected subgraph that contains all molecular determinants of a disease." http://science.sciencemag.org/content/347/6224/1257601 View in LinkedIn

BEYOND GENOMICS. "Genomic sequencing will, however, if performed in isolation, leave fundamental questions pertaining to genotype-phenotype relationships unresolved. The causal changes that connect genotype to phenotype remain generally unknown, especially for complex trait loci and cancer-associated mutations." https://lnkd.in/eUdRWEe View in LinkedIn

POLYCAUSALITY. "A disease is rarely a straightforward consequence of an abnormality in a single gene, but rather reflects the interplay of multiple molecular processes. The relationships among these processes are encoded in the interactome, a network that integrates all physical interactions within a cell, from protein-protein to regulatory protein–DNA and metabolic interactions." https://lnkd.in/eBGWbaG View in LinkedIn

NETWORKS AND SELECTIVE PRESSURE. "Genes with lower network centralities are more likely to evolve under positive selection (as inferred from divergence data). Surprisingly, polymorphism data yield results in the opposite direction than divergence data: Genes with higher centralities are more likely to have been targeted by recent positive selection during recent human evolution." http://gbe.oxfordjournals.org/content/7/4/1141.full View in LinkedIn

GENES AND MOLECULAR NETWORKS. "Genes vary in their likelihood to undergo adaptive evolution. The genomic factors that determine adaptability, however, remain poorly understood. Genes function in the context of molecular networks, with some occupying more important positions than others and thus being likely to be under stronger selective pressures." https://lnkd.in/eUfp5tg View in LinkedIn