Year: 2022

PART OF THE WHOLE. "The function of a protein is often tied to its interactions, and many proteins function as components of large multiprotein complexes. Multiprotein complexes also will connect to each other in a cell to carry out coordinated biological functions. Every cell has a network of protein interactions, where these connections within and between proteins and complexes yield insights into cellular states." https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0913-4 View in LinkedIn

MANY HUMAN INTERACTOMES. "How they are different and regulated is crucial for their understanding. Protein interaction networks are dynamic and context dependent. The differences in networks between cellular states are probably determined by key regulatory mechanisms for controlling these states." https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0913-4 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

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

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

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

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

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

INTERACTING MODULES. "If two disease modules overlap, local perturbations causing one disease can disrupt pathways of the other disease module as well, resulting in shared clinical and pathobiological characteristics." http://science.sciencemag.org/content/347/6224/1257601 View in LinkedIn

MODULES WITH SIMILARITY. "We find that disease pairs with overlapping disease modules display significant molecular similarity, elevated coexpression of their associated genes, and similar symptoms and high comorbidity. At the same time, non-overlapping disease pairs lack any detectable pathobiological relationships." http://science.sciencemag.org/content/347/6224/1257601 View in LinkedIn