A5090010970- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Gene Regulatory Network Analysis
- Genomics and Chromatin Dynamics
- SARS-CoV-2 and COVID-19 Research
- Machine Learning in Bioinformatics
- Pharmacogenetics and Drug Metabolism
- Metabolomics and Mass Spectrometry Studies
- Microbial Metabolic Engineering and Bioproduction
- Cell Image Analysis Techniques
- COVID-19 Clinical Research Studies
- Microbial Natural Products and Biosynthesis
- bioluminescence and chemiluminescence research
- Health, Environment, Cognitive Aging
- Advanced Fluorescence Microscopy Techniques
- Spaceflight effects on biology
- Synthesis and biological activity
- Advanced biosensing and bioanalysis techniques
- Cellular Mechanics and Interactions
- vaccines and immunoinformatics approaches
- Advanced Biosensing Techniques and Applications
- Multiple Sclerosis Research Studies
- Organ Transplantation Techniques and Outcomes
University Hospital Heidelberg
2021-2024
Heidelberg University
2021-2024
Universitat Politècnica de Catalunya
2020-2022
Institute for Research in Biomedicine
2020-2022
Many methods allow us to extract biological activities from omics data using information prior knowledge resources, reducing the dimensionality for increased statistical power and better interpretability. Here, we present decoupleR, a Bioconductor Python package containing computational these within unified framework. decoupleR allows flexibly run any method with given resource, including that leverage mode of regulation weights interactions, which are not in other frameworks. Moreover, it...
Extrapulmonary manifestations of COVID-19 have gained attention due to their links clinical outcomes and potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart kidney. Whether it also directly affects liver has been debated2,3. Here we provide clinical, histopathological, molecular bioinformatic evidence for hepatic SARS-CoV-2. We find that injury, indicated by a high frequency abnormal function...
Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, their target genes, so called TF regulons, can be coupled with computational algorithms to estimate activity TFs. However, interpret these findings accurately, regulons high reliability coverage are needed. In this study, we present evaluate collection created using CollecTRI meta-resource...
The growing availability of single-cell and spatially resolved transcriptomics has led to the development many approaches infer cell-cell communication, each capturing only a partial view complex landscape intercellular signalling. Here we present LIANA+, scalable framework built around rich knowledge base decode coordinated inter- intracellular signalling events from single- multi-condition datasets in both data. By extending unifying established methodologies, LIANA+ provides comprehensive...
Abstract Chemical descriptors encode the physicochemical and structural properties of small molecules, they are at core chemoinformatics. The broad release bioactivity data has prompted enriched representations compounds, reaching beyond chemical structures capturing their known biological properties. Unfortunately, not available for most which limits applicability to a few thousand well characterized compounds. Here we present collection deep neural networks able infer signatures any...
The Columbia Cancer Target Discovery and Development (CTD2) Center is developing PANACEA, a resource comprising dose-responses RNA sequencing (RNA-seq) profiles of 25 cell lines perturbed with ∼400 clinical oncology drugs, to study tumor-specific drug mechanism action. Here, this serves as the basis for DREAM Challenge assessing accuracy sensitivity computational algorithms de novo polypharmacology predictions. Dose-response perturbational 32 kinase inhibitors are provided 21 teams who blind...
ABSTRACT Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, their target genes, so called TF regulons, can be coupled with computational algorithms to estimate activity TFs. However, interpret these findings accurately, regulons high reliability coverage are needed. In this study, we present evaluate collection created using CollecTRI...
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation gradually compartmentalized and restricted to specific tissue niches such as lesion rim. However, precise cell type composition niches, their interactions changes between active inactive stages are incompletely understood. We used single-nucleus spatial transcriptomics from subcortical MS corresponding control tissues map types associated pathways nonlesion areas. identified perivascular...
Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate impact spaceflight on mouse brain in female mice. Our comparative analysis between ground control spaceflight-exposed animals revealed alterations essential processes including...
Abstract Multiple sclerosis (MS) is a prototypic chronic-inflammatory disease of the central nervous system. After initial lesion formation during active demyelination, inflammation gradually compartmentalized and restricted to specific tissue areas such as rim in chronic-active lesions. However, cell type-specific spatially drivers chronic damage expansion are not well understood. Here, we investigated properties subcortical white matter lesions by creating spatial map gene expression...
Transcriptomics is widely used to assess the state of biological systems. There are many tools for different steps, such as normalization, differential expression, and enrichment. While numerous studies have examined impact method choices on expression results, little attention has been paid their effects further downstream functional analysis, which typically provides basis interpretation follow-up experiments. To address this, we introduce FLOP, a comprehensive nextflow-based workflow...
SUMMARY The Columbia Cancer Target Discovery and Development (CTD 2 ) Center has developed PANACEA (PANcancer Analysis of Chemical Entity Activity), a collection dose-response curves perturbational profiles for 400 clinical oncology drugs in cell lines selected to optimally represent 19 cancer subtypes. This resource, study tumor-specific drug mechanism action, was instrumental hosting DREAM Challenge assess computational models de novo polypharmacology prediction. Dose-response 32 kinase...
Background Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function poor outcomes. Remote ischemic preconditioning (RIPC) a simple, noninvasive procedure aimed at reducing IRI improving function. Experimental studies have implicated the kynurenine pathway as protective mechanism behind RIPC. Methods First, paired biopsies from 11 living donors were analyzed to characterize acute transcriptomic response...
Cells regulate their functions through gene expression, driven by a complex interplay of transcription factors and other regulatory mechanisms that together can be modeled as networks (GRNs). The emergence single-cell multi-omics technologies has the development several methods integrate transcriptomics chromatin accessibility data to infer GRNs. While these provide examples utility in discovering new interactions, comprehensive benchmark evaluating mechanistic predictive properties well...
<title>Abstract</title> Impairment of the central nervous system (CNS) functions in astronauts is a major health risk for long-duration space missions. Here, first time, we combine single-cell multiomics (transcriptomics and chromatin accessibility) spatial transcriptomics analyses to discover spaceflight-mediated changes mouse brain. By comparing ground control spaceflight animals, found that main processes affected by include neurogenesis, synaptogenesis synaptic transmission cortex,...
Abstract Transcriptomics, and in particular RNA-Seq, has become a widely used approach to assess the molecular state of biological systems. To facilitate its analysis, many tools have been developed for different steps, such as filtering lowly expressed genes, normalisation, differential expression, enrichment. While numerous studies examined impact method choices on expression results, little attention paid their effects further downstream functional analysis using enrichment gene sets,...
Abstract Chemical descriptors encode the physicochemical and structural properties of small molecules, they are at core chemoinformatics. The broad release bioactivity data has prompted enriched representations compounds, reaching beyond chemical structures capturing their known biological properties. Unfortunately, ‘bioactivity descriptors’ not available for most which limits applicability to a few thousand well characterized compounds. Here we present collection deep neural networks able...
Until a vaccine becomes available, the current repertoire of drugs is our only therapeutic asset to fight SARS-CoV-2 outbreak. Indeed, emergency clinical trials have been launched assess effectiveness many marketed drugs, tackling decrease viral load through several mechanisms. Here, we present an online resource, based on small-molecule bioactivity signatures and natural language processing, expand portfolio compounds with potential treat COVID-19. By comparing set reported be potentially...
The Columbia Cancer Target Discovery and Development (CTD2) Center has developed PANACEA (PANcancer Analysis of Chemical Entity Activity), a collection dose-response curves perturbational profiles for 400 clinical oncology drugs in cell lines selected to optimally represent 19 cancer subtypes. This resource, study tumor-specific drug mechanism action, was instrumental hosting DREAM Challenge assess computational models de novo polypharmacology prediction. Dose-response 32 kinase inhibitors...
We present an online resource, based on small-molecule bioactivity signatures and natural language processing, to expand the portfolio of compounds with potential treat COVID-19. By comparing set drugs reported be potentially active against SARS-CoV-2 a universe 1M bioactive molecules, we identify that display analogous chemical functional features current COVID-19 candidates. Searches can filtered by level evidence mechanism action, results restricted drug molecules or include much broader...
Abstract Summary Many methods allow us to extract biological activities from omics data using information prior knowledge resources, reducing the dimensionality for increased statistical power and better interpretability. Here, we present decoupleR, a Bioconductor package containing computational these within unified framework. decoupleR allows flexibly run any method with given resource, including that leverage mode of regulation weights interactions. Using evaluated performance on...
We present an online resource, based on small-molecule bioactivity signatures and natural language processing, to expand the portfolio of compounds with potential treat COVID-19. By comparing set drugs reported be potentially active against SARS-CoV-2 a universe 1M bioactive molecules, we identify that display analogous chemical functional features current COVID-19 candidates. Searches can filtered by level evidence mechanism action, results restricted drug molecules or include much broader...