- by Ding, J., Yoon, B., Raghavan, V.RNA velocity enables inference of cell state transitions from single-cell transcriptomics by modeling transcriptional dynamics from spliced and unspliced mRNA. However, existing methods overlook spatial context and struggle to scale to large datasets, limiting insights into tissue organization and dynamic processes. We introduce veloAgent, a deep generative and agent-based framework that estimates gene- and cell-specific transcriptional kinetics while integrating spatial information through agent-based simulations of local microenvironments. By leveraging both molecular and spatial cues, veloAgent improves velocity accuracy and achieves […]
- by Srinivasan, S., Kumar, S., Chatterjee, S., Chande, A.Circular RNA (circRNA) interacts with miRNAs and proteins and can regulate various cellular processes. Compared to circRNA-miRNA interaction, circRNA-protein interaction (CPI) has been relatively less explored, following which we developed a comprehensive user-friendly web resource, circDiscoverer, which provides an open-access knowledge base empowering characterization of circRNA-protein interactions in Homo sapiens. circDiscoverer contains manually curated circRNA-protein interactions from published articles and predicted circRNA-protein interactions. Furthermore, the resource offers comprehensive insights into protein binding profiles and presents detailed information on interacting circRNAs, […]
- by Shukla, A. K., Dayama, B. R., Nikam, S. S., Kadoo, N.Pectin methylesterases (PMEs) are key regulators of plant cell wall remodeling; however, their evolutionary dynamics and stress-responsive roles remain poorly understood in cucurbit crops. This study aimed to systematically characterize the PME gene family in cucumber (Cucumis sativus) and muskmelon (Cucumis melo), addressing how PME diversification, duplication, and regulatory architecture underpin their responses to biotic and abiotic stresses. Using a Hidden Markov Model-based genome-wide screening approach, we identified 52 PME genes in cucumber and 56 in muskmelon, which were classified […]
- by Montalvo-Arredondo, J., Juarez-Verdayes, M. A.The Fabaceae plants (Legumes) are important for the economy and food sovereignty of Mexico. Traits development of agronomic interest, and other biological activities of the Fabaceae plants are tightly related to the gene regulation, like the post-transcriptional gene repression mediated by microRNAs. Several artificial intelligence models have been developed for the miRNA precursor sequence prediction. They were based mainly on Convolutional Neural Network and Multi-Layer Perceptron architectures. Although the numerical encoding of nucleotide sequence and its secondary structure of pre-miRNAs […]
- by Xu, H., Bandeira, N.Spectral library search (SLS) is a major approach for peptide identification from tandem mass spectrometry data, with performance depending substantially on the accuracy of the underlying Spectrum-Spectrum Matching (SSM) scoring functions. However, detailed comparative studies remain limited by the absence of comprehensive benchmark datasets. We propose new methods to build SSM scoring functions benchmarks and construct a benchmark dataset with (i) eight query spectrum sets with varying noise level for 476,063 precursors, and (ii) three spectral libraries with experimental, de-noised […]
- by Dong, M., Adduri, A., Gautam, D., Carpenter, C., Shah, R., Ricci-Tam, C., Kluger, Y., Burke, D. P., Roohani, Y. H.Single-cell transcriptomics offers the promise of measuring the diversity of cellular phenotypes across species, diseases, and other biological conditions. Recently, foundation models have emerged to identify this variation, yet most methods represent each cell independently, despite technical limitations that reduce measurement precision at the single-cell level. Here, we present Stack, a foundation model trained on 149 million uniformly preprocessed human single cells that leverages tabular attention to generate representations for each cell informed by the cells in its context. Stack […]
- by Montgomery, T. L., Nelson, E. A., Downs, L. A., Heney, E. R., Lee, M. F. J., Martino, C., McDonald, D., Rahman, G., Knight, R., Krementsov, D. N.Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) driven by genetic and environmental determinants. The gut microbiome of people with MS (pwMS) is distinct and influences disease through immunomodulatory metabolite production. Circulating metabolites are altered in pwMS, but identifying microbial-metabolic drivers remains challenging. We previously showed that colonization by the gut commensal Limosilactobacillus reuteri (L. reuteri) exacerbates disease in the experimental autoimmune encephalomyelitis (EAE) model of MS, in a tryptophan-dependent manner. Here, we integrated microbiomic […]
- by Wang, Z., Lei, Z., Chen, R.Helicobacter pylori infection is a primary risk factor for gastric carcinogenesis, yet the heterogeneity of host cellular responses remains incompletely characterized. This study systematically delineates the transcriptional landscapes of four gastric epithelial cell lines (AGS, GES-1, HGC-27, MKN-45) upon H. pylori infection. Transcriptomic analyses revealed distinct, cell-type-specific dysregulation patterns, with Gene Ontology enrichment highlighting perturbations in processes ranging from epidermal differentiation and metabolism (AGS) to extracellular matrix remodeling (GES-1), cell cycle control (HGC-27), and mitotic regulation (MKN-45). Intersection analysis identified […]
- by Hemminger, Z., De Ocampo, H., Xie, F., Zhai, Z., Li, J. J., Wollman, R.Motivation: Most spatial transcriptomics methods measure individual genes, which limits scalability and typically requires integration with scRNA-seq to recover full cellular states. Recent approaches such as CISI, FISHnCHIPs, and ATLAS address this by measuring aggregate transcriptional signatures, where multiple genes are pooled into each channel to increase throughput. While aggregate measurements improve scalability, they shift the problem from gene selection to feature design. For effective integration with scRNA-seq, these signatures must be not only discriminative in transcriptional space but also […]
- by Zelic, M., Gligorovski, V., Labbaf, F., Labagnara, M., Oesterle, R., Brenna, G., Massard, F., Chethan, S. G., Li, W., Martin, S. G., Hauf, S., Rahi, S. J.Tracking and lineage tracing are widely needed tasks in biological image analysis. For cells that grow and divide, tracking is challenging because cells change in number, shape, and size throughout a recording. As the time interval between images increases, it becomes more difficult to establish correspondences between cells across timepoints. Consequently, tracking has to be performed between consecutive or temporally close images, which leads to exponentially decreasing tracking accuracy and thus high sensitivity to error rates. For budding yeast, this […]
- by Chatelain, Y. M. B., Sokołowski, A., Sharp, M., Poline, J.-B., Glatard, T.Numerical variability is rarely quantified in neuroimaging despite many biomarkers relying on subtle morphometric differences across individuals. We instrumented FreeSurfer, a widely used neuroimaging pipeline, to simulate numerical differences across computational environments, and used it to measure numerical variability in MRI analyses of Parkinson's disease patients and controls. In multiple cortical and subcortical regions, numerical variation reached nearly one-third of the population variability, altering statistical conclusions about group differences and clinical associations. To address this, we developed a practical tool […]
- by Zhang, Z., Ren, W., Xie, L., Zheng, Y., Guan, X., Wang, J., Li, W., Tang, Q.-Y.The interplay between protein folding and native dynamics remains a central question in biophysics. Analyzing an extensive set of AlphaFold-predicted structures, we uncover a robust relationship between folding topology (contact order) and native dynamics (fluctuation entropy), showing that long-range contacts that slow folding also restrict conformational flexibility across protein sizes and taxonomic groups. Scaling analysis reveals that this relationship, together with its chain-length dependence, is consistent with power-law-like trends, reflecting common organizing constraints of protein architecture. Across species, increasing organismal […]
- by Altendorfer, S., Walker, S. J., Daub, C. O.Background Spot-based Spatial transcriptomics (ST) allows for unbiased gene expression analysis within tissue architecture, overcoming the limitations of single-cell RNA sequencing (scRNA-seq) by preserving spatial context. However, the high spatial resolution in ST leads to cellular heterogeneity within spots, requiring computational deconvolution to infer cellular compositions. While scRNA-seq serves as a key reference for deconvolution, the impact of reference composition on its accuracy is still unclear. In this study, we systematically evaluate the impact of reference selection for cellular deconvolution […]
- by Ma, H., Wang, D.Spatial sequencing technologies enable the study of molecular organization, such as gene and protein expression, at single-cell resolution. Revealing such spatial patterns relies on accurate cell segmentation. Particularly, in complex tissues with dense cell packing, segmentation based solely on nuclear staining is insufficient for accurate cell boundary detection. This limitation arises because accurate segmentation necessitates the delineation of cell morphology, which is driven by molecular activities such as cytoskeletal dynamics, cell-cell adhesion, and intercellular signaling. Thus, integrating molecular information, such […]
- by Bissoondial, T. L., Reddi, R., Madugula, S. S., Shukla, M., Narayan, M., Narayan, P.The risk for hepatocellular carcinoma (HCC) arising from metabolic dysfunction-associated steatotic liver disease (MASLD)-related cirrhosis exceeds the risk for cancer developing in the kidney, heart, or lung as a consequence of end-stage disease in those organs. Both experimental and clinical studies support the existence of circulating biomarkers whose elevated expression is associated with, and supports the diagnosis of, HCC. We posit the existence of oncogenic HCC biomarkers under regulation by tumor-suppressive microRNAs (miRs), and that reduced tumor-suppressive miR expression leads […]
- by Koddenbrock, M., Westerhoff, J., Fachet, D., Reber, S., Gers, F., Rodner, E.Studying microtubules (MTs) and their mechanical properties is central to understanding intracellular transport, cell division, and drug action. While important, experts still need to spend many hours manually segmenting these filamentous structures. The suitability of state-of-the-art methods for this task cannot be systematically assessed, as large-scale labeled datasets are missing. We address this gap by presenting the synthetic dataset SynthMT, produced by tuning a novel image generation pipeline on real-world interference reflection microscopy (IRM) frames of in vitro reconstituted MTs […]
- by Richardson, E., Lischwe, P., Bennett, J., Blazeska, N., Greenbaum, J., Harlan, B., Lallmamode, N., Marrama, D., Talbott, M., Vita, R., Sette, A., Kuether, K., Peters, B.The Immune Epitope Database (IEDB, iedb.org) has manually curated epitope data from over 26,000 publications across two decades. With PubMed adding ~5,000 articles daily, traditional curation methods face scalability challenges. Given the multimodality of data contained in scientific papers, we have sought to build an open-source vision language model (VLM)-based tool that human curators can use to speed up and automate biological data curation. Here we present a multimodal document ingestion and Question-Answering (QnA) pipeline that ties traditional Optical Character […]
- by Malhotra, S., Ward, A., Giles, L., Gerrard, T., Winn, M., Holden, N. J.The genetic diversity of the Shiga toxin-producing Escherichia coli (STEC) sub-species group poses major challenges for assigning pathogenic potential, and for accurate diagnostics. Although existing risk-based frameworks work for the predominant serotypes e.g. STEC O157 or O26, they are less useful for more diverse genotypes, with variation in the genetic complement of virulence factors that is responsible for disease outcome. Moreover, genetic diversity occurs at the virulence factor allele level. We investigated the functional potential of genetic variation at a […]
- by Crego-Walters, M., Cuadros-Espinoza, S., Ruiz-Gartzia, I., Han, S., Hermosilla, N., Helsen, P., Frandsen, P., Brumwell Prats, A. M., Alentorn-Moron, P., Fontsere, C., Alvarez Estape, M., Ngofuna, M., Monghiemo, C., Leendertz, F., Thompson, J., Fasbender, D., Dieguez, P., Lotana Lokasola, A., Brand, C., Ndjango, J.-B., Georgiev, A. V., Giles, J. A., Liu, W., Li, Y., Sharp, P. M., Pereboom, Z., Andres, A. M., Kuhlwilm, M., Gronau, I., Kuehl, H., Wessling, E. G., Narat, V., Surbeck, M., Hart, J. A., Hart, T. B., Hvilsom, C., Krutzen, M., Stevens, J., Hahn, B. H., Lizano, E., Prado-Martinez, J., MBonobos (Pan paniscus), an endangered species, have for decades been genetically understudied, partly due to difficulties in obtaining high-quality samples. The study of their genome is important not only for understanding their evolution, but also for improving conservation efforts, including population management, diversity and inbreeding assessment, and tracking rescued individuals to combat illegal wildlife trafficking. Here, we use chromosome 21 target capture data from 156 non-invasively collected faecal samples from wild bonobos to perform a comprehensive analysis of their population […]
- by Bera, I., Fernandez-Diaz, R., O Sullivan, M., Jacquir, J.-C., Scaife, C., Litovskich, G., Wynne, K., Shields, D.We investigated how seed proteolysis was enhanced by germination, by subsequent homogenisation (disrupting sprout compartments), and by co-incubation of homogenates from different species. Mass spectrometry of released peptides tracked proteolytic signatures from chickpea, lentil, mung and broccoli proteins, in soaked seeds, in sprouted seeds, and after sprout homogenisation followed by incubation alone or in mixture with other sprouts. The proteolytic signatures differed markedly among the four species, and in the different treatment conditions. After homogenisation, legumain-like cleavage (after asparagine) increased […]
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