State-of-the-art machine learning models in drug discovery fail to reliably predict the binding properties of poorly annotated proteins and small molecules. Here, the authors present AI-Bind, a machine learning pipeline to improve generalizability and interpretability of binding predictions.

Abstract The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome.

Abstract Network Medicine has improved the mechanistic understanding of disease, offering quantitative insights into disease mechanisms, comorbidities, and novel diagnostic tools and therapeutic treatments. Yet, most network-based approaches rely on a comprehensive map of protein-protein interactions, ignoring interactions mediated by non-coding RNAs (ncRNAs). Here, we systematically combine experimentally confirmed binding interactions mediated by ncRNA with protein-protein interactions, constructing the first comprehensive network of all physical interactions in the human cell.

Abstract Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6,710 clinical and preclinical compounds targeting 2,183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target, and cell interactome produced cellular networks important for infection.

Abstract The nosographic structure of posttraumatic stress disorder (PTSD) remains unclear, and attempts to determine its symptomatic organization have been unsatisfactory. Several explanations have been suggested, and the impact of trauma type is receiving increasing attention. As little is known about the differential impact trauma type in the nosographic structure of PTSD, we explored the nosology of PTSD and the effect of trauma type on its symptomatic organization. We reanalyzed five cross-sectional psychopathological networks involving different trauma types, encompassing a broad range of traumatic events in veterans, war-related trauma in veterans, sexual abuse, terrorist attacks, and various traumatic events in refugees.

Abstract Earthworms are considered ecosystem engineers due to their fundamental impact on soil structure, soil processes and on other soil biota. An invasion of non-native earthworm species has altered soils of North America since European settlement, a process currently expanding into still earthworm-free forest ecosystems due to continuous spread and increasing soil temperatures owing to climate change. Although earthworms are known to modify soil microbial diversity and activity, it is as yet unclear how eukaryote consumers in soil microbial food webs will be affected.

The European green lizards of the Lacerta viridis complex consist of two closely related species, L. viridis and L. bilineata that split less than 7 million years ago in the presence of gene flow. Recently, a third lineage, referred to as the “Adriatic” was described within the L. viridis complex distributed from Slovenia to Greece.

The COVID-19 pandemic has highlighted the importance of prioritizing approved drugs to treat severe acute respiratory syndrome coronavirus (SARS-CoV-2) infections. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity to rank 6,340 drugs for their expected efficacy against SARS-CoV-2.

A new analysis traces the story of the draft genome’s impact on genomics since 2001, linking its effects on publications, drug approvals and understanding of disease.

Here we present a method for the systematic comparison of an unlimited number of networks, with unlimited number of transcripts: Co-expression Differential Network Analysis (CoDiNA).