CosMxScope: Scalable Reconstruction and Digital Pathology Integration of Imaging-Based Spatial Transcriptomics Data

This paper introduces CosMxScope, an open-source Python framework that bridges the gap between CosMx Spatial Molecular Imager data and digital pathology tools by stitching image tiles, converting spatial coordinates into GeoJSON for QuPath compatibility, and enabling interactive visualization of gene expression alongside cell morphology.

Chen, J., Isett, B., Gu, Q. + 1 more2026-03-30💻 bioinformatics

Track Hub Quickload Translator: Convert Track Hub or Quickload data for viewing in the UCSC Genome Browser or the Integrated Genome Browser

The Track Hub Quickload Translator is a freely available Python-based web application that converts data between UCSC Genome Browser track hubs and Integrated Genome Browser Quickload formats, enabling researchers to visualize tens of thousands of published genome assemblies in either browser.

Freese, N. H., Raveendran, K., Sirigineedi, J. S. + 7 more2026-03-30💻 bioinformatics

Evolutionary history of ligand binding by the LRR domain of innate immunity receptors: the story of the TLR2 cavity

This study utilizes AI protein structure predictions to demonstrate that the hydrophobic ligand-binding cavity in vertebrate TLR2 is an evolutionarily conserved feature essential for pathogen recognition, while revealing that similar cavities in invertebrate TLRs and other LRR domains arose through independent convergent evolution rather than shared ancestry.

Namou, R., Ichii, K., Takkouche, A. + 2 more2026-03-30💻 bioinformatics

Evolutionary exploration of drug-like chemical space utilizing generative AI and virtual screening

This paper presents an evolutionary AI framework that integrates generative models, reaction-based substructure searching, and iterative fine-tuning to efficiently navigate ultra-large chemical spaces, successfully identifying and validating novel, synthetically accessible ligands for the μ\mu-opioid receptor within the Enamine REAL Space.

Secker, C., Secker, P., Yergoez, F. + 11 more2026-03-30💻 bioinformatics

Deciphering sepsis molecular subtypes using large-scale data to identify subtype-specific drug repurposing

By constructing a transcriptomic atlas of 3,713 samples to identify four distinct molecular subtypes of sepsis, this study elucidates subtype-specific pathophysiological mechanisms and proposes targeted drug repurposing strategies, such as corticosteroids for C1 and methylene blue for the high-mortality C4 subtype, to advance precision medicine and explain the failure of previous broad-spectrum clinical trials.

Smith, L. A., Augustin, B., Jacob, V. + 8 more2026-03-30💻 bioinformatics

DeepBranchAI: A Novel Cascade Workflow Enabling Accessible 3D Branching Network Segmentation

DeepBranchAI introduces a novel cascade workflow that overcomes the annotation bottleneck in 3D branching network segmentation by iteratively refining sparse labels through a positive feedback loop of random forests and expert input, ultimately enabling the training of a robust, topology-preserving 3D nnU-Net model that achieves high accuracy across diverse biological and medical datasets while significantly reducing manual annotation time.

Maltsev, A. V., Hartnell, L., Ferrucci, L.2026-03-29💻 bioinformatics

A run-length-compressed skiplist data structure for dynamic GBWTs supports time and space efficient pangenome operations over syncmers

This paper introduces a dynamic, run-length-compressed skiplist data structure for the graph Burrows-Wheeler transform (GBWT) that enables time and space-efficient pangenome operations on syncmer graphs, successfully building a 5.8 GB lossless representation of 92 human genomes in under an hour and supporting rapid sequence matching.

Durbin, R.2026-03-29💻 bioinformatics

Inverse signal importance in real exposome: How do biological systems dynamically prioritize multiple environmental signals?

This study introduces a machine learning framework called Inverse Signal Importance (ISI) to analyze how medaka fish dynamically prioritize multiple environmental signals for gonadal development in natural settings, revealing complex adaptive mechanisms that are often missed in controlled laboratory studies.

Itoh, T., Kondo, Y., Nakayama, T. + 4 more2026-03-28💻 bioinformatics

Open-source, Hardware-Independent GPU Acceleration for Scalable Nanopore Basecalling with Slorado and Openfish

This paper introduces Openfish, an open-source GPU-accelerated decoding library, and Slorado, a fully open-source basecalling framework, to provide a hardware-independent, scalable, and accurate alternative to Oxford Nanopore Technologies' proprietary Dorado software, thereby eliminating hardware lock-in and enhancing accessibility for nanopore sequencing.

Wong, B., Singh, G., Javaid, H. + 5 more2026-03-28💻 bioinformatics

scMagnifier: resolving fine-grained cell subtypes via GRN-informed perturbations and consensus clustering

scMagnifier is a consensus clustering framework that leverages gene regulatory network-informed in silico perturbations and a novel visualization method to amplify subtle transcriptional differences, thereby enabling the high-resolution identification and spatial mapping of fine-grained cell subtypes in both single-cell and spatial transcriptomics data.

He, Z., Kangning, D.2026-03-28💻 bioinformatics

A new iterative framework for simulation-based population genetic inference with improved coverage properties of confidence intervals

This paper introduces and evaluates a new iterative inference framework that combines random forests with multivariate Gaussian mixture models to improve the coverage properties of confidence intervals and estimator precision in population genetic simulations compared to non-iterative ABC-RF and sequential neural likelihood methods.

Rousset, F., Leblois, R., Estoup, A. + 1 more2026-03-27💻 bioinformatics