Domain-mediated interactions for protein subfamily identification

Within a protein family, proteins with the same domain often exhibit different cellular functions, despite the shared evolutionary history and molecular function of the domain. We hypothesized that domain-mediated interactions (DMIs) may categorize a protein family into subfamilies because the diversified functions of a single domain often depend on interacting partners of domains. Here we systematically identified DMI subfamilies, in which proteins share domains with DMI partners, as well as with various functional and physical interaction networks in individual species. In humans, DMI subfamily members are associated with similar diseases, including cancers, and are frequently co-associated with the same diseases. DMI information relates to the functional and evolutionary subdivisions of human kinases. In yeast, DMI subfamilies contain proteins with similar phenotypic outcomes from specific chemical treatments. Therefore, the systematic investigation here provides insights into the diverse functions of subfamilies derived from a protein family with a link-centric approach and suggests a useful resource for annotating the functions and phenotypic outcomes of proteins.11Ysciescopu

The BioGRID Interaction Database: 2011 update

The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein interaction data from model organisms and humans (http://www.thebiogrid.org). BioGRID currently holds 347 966 interactions (170 162 genetic, 177 804 protein) curated from both high-throughput data sets and individual focused studies, as derived from over 23 000 publications in the primary literature. Complete coverage of the entire literature is maintained for budding yeast (Saccharomyces cerevisiae), fission yeast (Schizosaccharomyces pombe) and thale cress (Arabidopsis thaliana), and efforts to expand curation across multiple metazoan species are underway. The BioGRID houses 48 831 human protein interactions that have been curated from 10 247 publications. Current curation drives are focused on particular areas of biology to enable insights into conserved networks and pathways that are relevant to human health. The BioGRID 3.0 web interface contains new search and display features that enable rapid queries across multiple data types and sources. An automated Interaction Management System (IMS) is used to prioritize, coordinate and track curation across international sites and projects. BioGRID provides interaction data to several model organism databases, resources such as Entrez-Gene and other interaction meta-databases. The entire BioGRID 3.0 data collection may be downloaded in multiple file formats, including PSI MI XML. Source code for BioGRID 3.0 is freely available without any restrictions

Protein-protein interactions: network analysis and applications in drug discovery

Physical interactions among proteins constitute the backbone of cellular function, making them an attractive source of therapeutic targets. Although the challenges associated with targeting protein-protein interactions (PPIs) -in particular with small molecules are considerable, a growing number of functional PPI modulators is being reported and clinically evaluated. An essential starting point for PPI inhibitor screening or design projects is the generation of a detailed map of the human interactome and the interactions between human and pathogen proteins. Different routes to produce these biological networks are being combined, including literature curation and computational methods. Experimental approaches to map PPIs mainly rely on the yeast two-hybrid (Y2H) technology, which have recently shown to produce reliable protein networks. However, other genetic and biochemical methods will be essential to increase both coverage and resolution of current protein networks in order to increase their utility towards the identification of novel disease-related proteins and PPIs, and their potential use as therapeutic targets

Massive MIMO is a Reality -- What is Next? Five Promising Research Directions for Antenna Arrays

Massive MIMO (multiple-input multiple-output) is no longer a "wild" or "promising" concept for future cellular networks - in 2018 it became a reality. Base stations (BSs) with 64 fully digital transceiver chains were commercially deployed in several countries, the key ingredients of Massive MIMO have made it into the 5G standard, the signal processing methods required to achieve unprecedented spectral efficiency have been developed, and the limitation due to pilot contamination has been resolved. Even the development of fully digital Massive MIMO arrays for mmWave frequencies - once viewed prohibitively complicated and costly - is well underway. In a few years, Massive MIMO with fully digital transceivers will be a mainstream feature at both sub-6 GHz and mmWave frequencies. In this paper, we explain how the first chapter of the Massive MIMO research saga has come to an end, while the story has just begun. The coming wide-scale deployment of BSs with massive antenna arrays opens the door to a brand new world where spatial processing capabilities are omnipresent. In addition to mobile broadband services, the antennas can be used for other communication applications, such as low-power machine-type or ultra-reliable communications, as well as non-communication applications such as radar, sensing and positioning. We outline five new Massive MIMO related research directions: Extremely large aperture arrays, Holographic Massive MIMO, Six-dimensional positioning, Large-scale MIMO radar, and Intelligent Massive MIMO.Comment: 20 pages, 9 figures, submitted to Digital Signal Processin

Typing tumors using pathways selected by somatic evolution.

Many recent efforts to analyze cancer genomes involve aggregation of mutations within reference maps of molecular pathways and protein networks. Here, we find these pathway studies are impeded by molecular interactions that are functionally irrelevant to cancer or the patient's tumor type, as these interactions diminish the contrast of driver pathways relative to individual frequently mutated genes. This problem can be addressed by creating stringent tumor-specific networks of biophysical protein interactions, identified by signatures of epistatic selection during tumor evolution. Using such an evolutionarily selected pathway (ESP) map, we analyze the major cancer genome atlases to derive a hierarchical classification of tumor subtypes linked to characteristic mutated pathways. These pathways are clinically prognostic and predictive, including the TP53-AXIN-ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we validate in independent cohorts. This ESP framework substantially improves the definition of cancer pathways and subtypes from tumor genome data

Inferring the Sign of Kinase-Substrate Interactions by Combining Quantitative Phosphoproteomics with a Literature-Based Mammalian Kinome Network

Protein phosphorylation is a reversible post-translational modification commonly used by cell signaling networks to transmit information about the extracellular environment into intracellular organelles for the regulation of the activity and sorting of proteins within the cell. For this study we reconstructed a literature-based mammalian kinase-substrate network from several online resources. The interactions within this directed graph network connect kinases to their substrates, through specific phosphosites including kinase-kinase regulatory interactions. However, the "signs" of links, activation or inhibition of the substrate upon phosphorylation, within this network are mostly unknown. Here we show how we can infer the "signs" indirectly using data from quantitative phosphoproteomics experiments applied to mammalian cells combined with the literature-based kinase-substrate network. Our inference method was able to predict the sign for 321 links and 153 phosphosites on 120 kinases, resulting in signed and directed subnetwork of mammalian kinase-kinase interactions. Such an approach can rapidly advance the reconstruction of cell signaling pathways and networks regulating mammalian cells.Comment: 5 page, 3 figures, IEEE-BIBE confrenc

Natural Language Does Not Emerge 'Naturally' in Multi-Agent Dialog

A number of recent works have proposed techniques for end-to-end learning of communication protocols among cooperative multi-agent populations, and have simultaneously found the emergence of grounded human-interpretable language in the protocols developed by the agents, all learned without any human supervision! In this paper, using a Task and Tell reference game between two agents as a testbed, we present a sequence of 'negative' results culminating in a 'positive' one -- showing that while most agent-invented languages are effective (i.e. achieve near-perfect task rewards), they are decidedly not interpretable or compositional. In essence, we find that natural language does not emerge 'naturally', despite the semblance of ease of natural-language-emergence that one may gather from recent literature. We discuss how it is possible to coax the invented languages to become more and more human-like and compositional by increasing restrictions on how two agents may communicate.Comment: 9 pages, 7 figures, 2 tables, accepted at EMNLP 2017 as short pape