The international consortium of scientists, led by Pascal Falter-Braun, Director at the Helmholtz Munich Institute of Network Biology (INET) and Professor at the Faculty of Biology, Ludwig-Maximilians-University (LMU) Munich, Germany, included teams in Canada, U.S., France, Spain and Belgium. The contact map, published in the journal Nature Biotechnology, reveals more than 200 direct protein-protein contacts, or protein interactions. What exactly are the molecular interactions between the virus causing COVID-19 and its human host? How might our genetic differences cause different disease courses? And how do still-emerging virus variants differ in their host-virus interactions? To get to the bottom of these questions, an international team of researchers has generated a systematic map of molecular contacts between the SARS-CoV-2 virus and its human host. d, Host targets identified in HuSCI overlap with RNA-binding proteins (RBPs) bound to SARS-CoV-2 RNA upon infection (left) and actual overlap (arrow) compared to n = 10,000 randomized control networks (right) (one-sided, empirical P = 0.007). c, Overlap of SARS-CoV-2 targets identified in HuSCI with previously identified target proteins of other viruses (left) and actual overlap (arrow) compared to n = 10,000 randomized control networks (right) (one-sided, empirical P < 0.0001). Asterisks indicate significant differences from vhRRS benchmark (* P = 0.023 ** P = 0.005 **** P = 1.57 × 10 −5 hsPRS-v2, P = 1.02 × 10 −7 HuSCI NS, not significant two-sided Fisher’s exact test center, proportion of positives error bars, standard error of proportion). b, Orthogonal validation fraction of pairs that are yN2H-positive in HuSCI (top, n = 282 pair configurations representing 148 HuSCIs interaction pairs) and IntraSCI (bottom, n = 41 pair configurations for 25 IntraSCI interaction pairs), in the benchmark positive control sets hsPRS-v2 ( n = 180 pair configurations for 60 interaction pairs) and vhLit-BM ( n = 164 pair configurations for 40 interaction pairs), and negative control sets hsRRS-v2 ( n = 234 pair configurations for 78 protein pairs) and vhRRS ( n = 360 pair configurations for 178 protein pairs). N, nucleocapsid protein S, spike protein. a, The contactome, the sum of physical contacts between viral and host macromolecules, mediates cellular perturbations that enable viral replication and cause disease manifestations. Generation and quality assessment of HuSCI.
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January 2023
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