Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis

Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2021

The National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), provides a suite of database resources to support worldwide research activities in both academia and industry. With the explosive growth of multiomics data, CNCB-NGDC is continually expanding, updating and enriching its core database resources through big data deposition, integration and translation. In the past year, considerable efforts have been devoted to 2019nCoVR, a newly established resource providing a global landscape of SARS-CoV-2 genomic sequences, variants, and haplotypes, as well as Aging Atlas, BrainBase, GTDB (Glycosyltransferases Database), LncExpDB, and TransCirc (Translation potential for circular RNAs). Meanwhile, a series of resources have been updated and improved, including BioProject, BioSample, GWH (Genome Warehouse), GVM (Genome Variation Map), GEN (Gene Expression Nebulas) as well as several biodiversity and plant resources. Particularly, BIG Search, a scalable, one-stop, cross-database search engine, has been significantly updated by providing easy access to a large number of internal and external biological resources from CNCB-NGDC, our partners, EBI and NCBI. All of these resources along with their services are publicly accessible at https://bigd.big.ac.cn