by Gisela Gabernet, Susanna Marquez, Robert Bjornson, Alexander Peltzer, Hailong Meng, Edel Aron, Noah Y. Lee, Cole Jensen, David Ladd, Mark Polster, Friederike Hanssen, Simon Heumos, nf-core community , Gur Yaari, Markus C. Kowarik, Sven Nahnsen, Steven H. Kleinstein Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and ..read more

by Eric Tatara, Qinyun Lin, Jonathan Ozik, Marynia Kolak, Nicholson Collier, Dylan Halpern, Luc Anselin, Harel Dahari, Basmattee Boodram, John Schneider Access to treatment and medication for opioid use disorder (MOUD) is essential in reducing opioid use and associated behavioral risks, such as syringe sharing among persons who inject drugs (PWID). Syringe sharing among PWID carries high risk of transmission of serious infections such as hepatitis C and HIV. MOUD resources, such as methadone provider clinics, however, are often unavailable to PWID due to barriers like long travel distance to t ..read more

by David Moreau, Kristina Wiebels Open science principles are revolutionizing the transparency, reproducibility, and accessibility of research. Meta-analysis has become a key technique for synthesizing data across studies in a principled way; however, its impact is contingent on adherence to open science practices. Here, we outline 9 quick tips for open meta-analyses, aimed at guiding researchers to maximize the reach and utility of their findings. We advocate for outlining preregistering clear protocols, opting for open tools and software, and the use of version control systems to ensure tran ..read more

by Patrick Bryant, Frank Noé Structure prediction of protein complexes has improved significantly with AlphaFold2 and AlphaFold-multimer (AFM), but only 60% of dimers are accurately predicted. Here, we learn a bias to the MSA representation that improves the predictions by performing gradient descent through the AFM network. We demonstrate the performance on seven difficult targets from CASP15 and increase the average MMscore to 0.76 compared to 0.63 with AFM. We evaluate the procedure on 487 protein complexes where AFM fails and obtain an increased success rate (MMscore>0.75) of 33% on the ..read more

by Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci Increasing genetic and phenotypic data size is critical for understanding the genetic determinants of diseases. Evidently, establishing practical means for collaboration and data sharing among institutions is a fundamental methodological barrier for performing high-powered studies. As the sample sizes become more heterogeneous, complex statistical approaches, such as generalized linear mixed effects models, must be used to correct for the confounders that may bias results. On another front, due to the privacy concerns around Protected Healt ..read more

by Pierre Le Denmat, Tom Verguts, Kobe Desender Human decision making is accompanied by a sense of confidence. According to Bayesian decision theory, confidence reflects the learned probability of making a correct response, given available data (e.g., accumulated stimulus evidence and response time). Although optimal, independently learning these probabilities for all possible data combinations is computationally intractable. Here, we describe a novel model of confidence implementing a low-dimensional approximation of this optimal yet intractable solution. This model allows efficient estimatio ..read more

by Virgile Andreani, Eric J. South, Mary J. Dunlop Dense arrangements of binding sites within nucleotide sequences can collectively influence downstream transcription rates or initiate biomolecular interactions. For example, natural promoter regions can harbor many overlapping transcription factor binding sites that influence the rate of transcription initiation. Despite the prevalence of overlapping binding sites in nature, rapid design of nucleotide sequences with many overlapping sites remains a challenge. Here, we show that this is an NP-hard problem, coined here as the nucleotide String P ..read more

by Noah B. Herrington, Yan Chak Li, David Stein, Gaurav Pandey, Avner Schlessinger Protein kinase function and interactions with drugs are controlled in part by the movement of the DFG and ɑC-Helix motifs that are related to the catalytic activity of the kinase. Small molecule ligands elicit therapeutic effects with distinct selectivity profiles and residence times that often depend on the active or inactive kinase conformation(s) they bind. Modern AI-based structural modeling methods have the potential to expand upon the limited availability of experimentally determined kinase structures in i ..read more

by Thomas Williams, James M. McCaw, James M. Osborne The role of direct cell–to–cell spread in viral infections—where virions spread between host and susceptible cells without needing to be secreted into the extracellular environment—has come to be understood as essential to the dynamics of medically significant viruses like hepatitis C and influenza. Recent work in both the experimental and mathematical modelling literature has attempted to quantify the prevalence of cell–to–cell infection compared to the conventional free virus route using a variety of methods and experimental data. However ..read more

by Simon K. S. Chu, Kush Narang, Justin B. Siegel Protein stability plays a crucial role in a variety of applications, such as food processing, therapeutics, and the identification of pathogenic mutations. Engineering campaigns commonly seek to improve protein stability, and there is a strong interest in streamlining these processes to enable rapid optimization of highly stabilized proteins with fewer iterations. In this work, we explore utilizing a mega-scale dataset to develop a protein language model optimized for stability prediction. ESMtherm is trained on the folding stability of 528k na ..read more