Biology subjects

Fisher, S.

Publications and source records attributed to Fisher, S..

At least 19 recordsLinked to original sources

bioRxiv2026

A small RNA guides a post-transcriptional regulatory protein to its target

RNA-binding proteins are central to post-transcriptional regulation and are generally thought to recognize their target RNAs through direct binding. Here, we uncover a previously unrecognized mechanism in which a small RNA (sRNA) guides a protein regulator to specific target mRNAs, enabling programmable post-transcriptional control. By mapping in pathogenic Escherichia coli the RNA interactome of CsrA, a global post-transcriptional regulator, we identify ~800 ternary complexes in which CsrA simultaneously binds an sRNA and an mRNA. Focusing on one class of these complexes, we show that PasE, a newly discovered sRNA, directs CsrA to virulence-associated mRNAs that are otherwise not targeted by CsrA, resulting in their repression. Altering the PasE seed sequence redirects CsrA to selected mRNAs, establishing a modular RNA-guided platform for gene regulation. Together, our findings reveal a new and likely widespread mechanism of bacterial post-transcriptional regulation and provide a framework for a new type of RNA-based synthetic regulation.

microbiology↗

bioRxiv2026

Structural Context Determines Docking Engine Performance: A Family-Stratified Benchmark of Six Engines

Molecular docking and co-folding engines are widely used to prioritize compounds for wet-lab validation, yet their accuracy is known to vary substantially across protein targets for reasons that remain only qualitatively understood. Here we benchmark six docking and co-folding engines (RevDock, DiffDock, Boltz2, AutoDock-GPU, rDock, and PandaDock) across 14 protein families, evaluating scoring power, ranking power, docking power, and physical validity. Rather than treating engine performance as protein-family-specific, we classify all 14 families into six mechanistic groups according to which of four scoring-function simplifications, rigid receptor, pairwise additivity, fixed point charges, and implicit solvent, is most severely stressed by that familys binding site. This framework helps explain, rather than simply describe, where each engine succeeds or fails: RevDocks CNN rescoring layer mitigates the pairwise additivity and fixed-charge limitations relative to physics-only scoring, achieving the highest overall pose accuracy (73.3% of poses [≤] 2.0 [A] RMSD), while Boltz2s sequence-based co-folding bypasses the rigid-receptor assumption and achieves comparable affinity correlation (mean Pearson r {approx} 0.60 for both engines). PandaDock, run with expanded conformational sampling, matches RevDock on pose accuracy (72.1% of poses [≤] 2.0 [A], lowest median RMSD at 0.96 [A]) and exceeds AutoDock-GPU on affinity correlation (mean r = 0.460), indicating that the performance of a physics-based scoring function is limited as much by search adequacy as by the scoring function itself. These results suggest that engine selection for a docking or co-folding campaign should be guided less by an engines aggregate benchmark ranking and more by which of these four structural and physical characteristics dominate the target of interest.

biochemistry↗

bioRxiv2026

Transcriptomic, Genomic, and Clinical Characterization of Morphological Classes in Localized and Metastatic Pancreatic Cancer

BackgroundHistomorphology is a strong prognostic biomarker correlated with basal-like and classical programs in surgically resected pancreatic ductal adenocarcinoma (PDAC). However, the spectrum of morphology and its biological associations remain poorly defined in advanced disease. ObjectivesWe explored the transcriptomic and genomic underpinnings and clinical relevance of morphological classes across localized and metastatic PDAC. DesignWe unified morphological classifications into four classes: glandular, cribriform, solid, and squamous. We integrated transcriptome and whole-genome sequencing following laser-capture microdissection with morphological classifications in 348 PDAC patients, where half of the cohort included locally advance and metastatic stages to uncover molecular associations. ResultsNon-glandular morphologies comprised three distinct classes that were enriched in metastatic disease. Transcriptomic profiling exhibited that glandular tumours predominantly expressed classical epithelial programs, although a subset displayed partial or full epithelial- mesenchymal transition signatures. In contrast, non-glandular morphologies showed basal-like transcriptional programs with subtype-specific pathways, including ciliogenesis in cribriform tumours, extracellular matrix remodelling and immune evasion in solid tumours, and keratinisation programs in squamous tumours. The solid class was significantly enriched in liver metastatic lesions and was associated with increased intra-tumoural morphological heterogeneity, whole-genome doubling, KRAS major allelic imbalance, and elevated KRAS-ERK signalling. ConclusionNon-glandular morphologies identify biologically distinct PDAC tumour states that are enriched in liver metastases and associated with subtype-specific transcriptional programs and KRAS-driven genomic alterations.

cancer biology↗

bioRxiv2025

Microbiota-derived indole metabolites inhibit rotavirus infection in vitro and in vivo and in human infants

Rotavirus (RV) is the leading cause of life-threatening gastroenteritis in children under five despite effective RV vaccines availability, necessitating novel protective strategies for high-risk populations. Gut microbiota can modulate RV susceptibility and vaccine immunogenicity, yet underlying mechanisms are poorly characterized. Here, we demonstrate that microbiota-derived indole metabolites confer protection against RV infection. In healthy adults, higher fecal indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) levels associated with reduced fecal RV shedding following challenge. In human intestinal enteroids (HIEs), IAA pre-treatment inhibited human RV Wa G1P[8] replication via the aryl hydrocarbon receptor (AhR) pathway. In mice, treatment with AhR agonist indole-3-carbinol (I3C) significantly reduced fecal shedding of murine RV strain EDIM-Cambridge. Finally, Zambian infants with active RV infection exhibited lower fecal IAA and IPA levels than age-matched healthy controls. These findings demonstrate that microbiota-derived AhR ligands consistently inhibit RV infection across three experimental models and hold promise for protecting at-risk pediatric populations.

microbiology↗

bioRxiv2025

Evaluating Multiomics Integration Architectures for Training With Structured Missingness

Multimodal bioinformatics datasets are increasingly common in biomedical research, for tasks such as cancer subtyping and outcome prediction. It is feasible that data from a given patient, or even all data from a given institution, does not have coverage across all modalities; the available data is contingent on both the assay choice at the institution alongside technical aspects and associated drop-out. Consequently, algorithms for machine learning models must be tolerant to structured data missingness (or occurrence) for entire modalities when training. In this paper, we compare general strategies for training multimodal models in the context of structured modality missingness, employing suitable strategies for the stage of modality integration: early by concatenation of features, intermediate by max pooling of latent features, and late by aggregating model predictions probabilistically. We evaluate our strategies on a real-world bioinformatics dataset for the task of breast cancer subtyping, constructing a range of structured missingness scenarios. We highlight that, despite their inability to learn cross-modality interactions, late integration models outperform against early and intermediate integration strategies across a range of scenarios according to the level and nature of missingness. Logistic regression models, although simple, also outperform neural networks within the same settings. Fundamentally, we show that understanding the structure of missingness within a dataset is necessary when selecting a method of integration, and that simple models and approaches should not be dismissed when working with structured missingness.

bioinformatics↗

bioRxiv2024

Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung

Understanding the mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis - the leading cause of cancer-related death. Using whole animal screens in genetically engineered mouse models of cancer we have identified circulating metabolites associated with metastasis. Specifically, we highlight the pyrimidine uracil as a prominent metastasis-associated metabolite. Uracil is generated by neutrophils expressing the enzyme uridine phosphorylase-1 (UPP1), and neutrophil specific Upp1 expression is increased in cancer. Altered UPP1 activity influences expression of adhesion molecules on the surface of neutrophils, leading to decreased neutrophil motility in the pre-metastatic lung. Furthermore, we find that UPP1-expressing neutrophils suppress T-cell proliferation, and the UPP1 product uracil can increase fibronectin deposition in the extracellular microenvironment. Consistently, knockout or inhibition of UPP1 in mice with mammary tumours increases the number of T-cells and reduces fibronectin content in the lung and decreases the proportion of mice that develop lung metastasis. These data indicate that UPP1 influences neutrophil behaviour and extracellular matrix deposition in the lung and suggest that pharmacological targeting of this pathway could be an effective strategy to reduce metastasis.

cancer biology↗

bioRxiv2024

A large-scale optogenetic neurophysiology platform for improving accessibility in NHP behavioral experiments

Optogenetics has been a powerful scientific tool for two decades, yet its integration with non-human primate (NHP) electrophysiology has been limited due to several technical challenges. These include a lack of electrode arrays capable of supporting large-scale and long-term optical access, inaccessible viral vector delivery methods for transfection of large regions of cortex, a paucity of hardware designed for large-scale patterned cortical illumination, and limited designs for multi-modal experimentation. To address these gaps, we introduce a highly accessible platform integrating optogenetics and electrophysiology for behavioral and neural modulation with neurophysiological recording in NHPs. We employed this platform in two rhesus macaques and showcased its capability of optogenetically disrupting reaches, while simultaneously monitoring ongoing electrocorticography activity underlying the stimulation-induced behavioral changes. The platform exhibits long-term stability and functionality, thereby facilitating large-scale electrophysiology, optical imaging, and optogenetics over months, which is crucial for translationally relevant multi-modal studies of neurological and neuropsychiatric disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/600719v2_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@179542eorg.highwire.dtl.DTLVardef@85ab3aorg.highwire.dtl.DTLVardef@1ac8deeorg.highwire.dtl.DTLVardef@19a0831_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Single-Mitochondrion Sequencing Uncovers Distinct Mutational Patterns and Heteroplasmy Landscape in Mouse Astrocytes and Neurons.

BackgroundMitochondrial (mt) heteroplasmy can cause adverse biological consequences when deleterious mtDNA mutations accumulate disrupting normal mt-driven processes and cellular functions. To investigate the heteroplasmy of such mtDNA changes we developed a moderate throughput mt isolation procedure to quantify the mt single-nucleotide variant (SNV) landscape in individual mouse neurons and astrocytes In this study we amplified mt-genomes from 1,645 single mitochondria (mts) isolated from mouse single astrocytes and neurons to 1. determine the distribution and proportion of mt-SNVs as well as mutation pattern in specific target regions across the mt-genome, 2. assess differences in mtDNA SNVs between neurons and astrocytes, and 3. Study cosegregation of variants in the mouse mtDNA. Results1. The data show that specific sites of the mt-genome are permissive to SNV presentation while others appear to be under stringent purifying selection. Nested hierarchical analysis at the levels of mitochondrion, cell, and mouse reveals distinct patterns of inter- and intra-cellular variation for mt-SNVs at different sites. 2. Further, differences in the SNV incidence were observed between mouse neurons and astrocytes for two mt-SNV 9027:G>A and 9419:C>T showing variation in the mutational propensity between these cell types. Purifying selection was observed in neurons as shown by the Ka/Ks statistic, suggesting that neurons are under stronger evolutionary constraint as compared to astrocytes. 3. Intriguingly, these data show strong linkage between the SNV sites at nucleotide positions 9027 and 9461. f ConclusionThis study suggests that segregation as well as clonal expansion of mt-SNVs is specific to individual genomic loci, which is important foundational data in understanding of heteroplasmy and disease thresholds for mutation of pathogenic variants.

neuroscience↗

bioRxiv2023

Wnt binding to Coatomer proteins directs secretion on exosomes independently of palmitoylation

Wnt proteins are secreted hydrophobic glycoproteins that act over long distances through poorly understood mechanisms. We discovered that Wnt7a is secreted on extracellular vesicles (EVs) following muscle injury. Structural analysis identified the motif responsible for Wnt7a secretion on EVs that we term the Exosome Binding Peptide (EBP). Addition of the EBP to an unrelated protein directed secretion on EVs. Disruption of palmitoylation, knockdown of WLS, or deletion of the N-terminal signal peptide did not affect Wnt7a secretion on purified EVs. Bio-ID analysis identified Coatomer proteins as candidates responsible for loading Wnt7a onto EVs. The crystal structure of EBP bound to the COPB2 coatomer subunit, the binding thermodynamics, and mutagenesis experiments, together demonstrate that a dilysine motif in the EBP mediates binding to COPB2. Other Wnts contain functionally analogous structural motifs. Mutation of the EBP results in a significant impairment in the ability of Wnt7a to stimulate regeneration, indicating that secretion of Wnt7a on exosomes is critical for normal regeneration in vivo. Our studies have defined the structural mechanism that mediates binding of Wnt7a to exosomes and elucidated the singularity of long-range Wnt signalling.

molecular biology↗

bioRxiv2022

Identification of conserved skeletal enhancers associated with craniosynostosis risk genes

Craniosynostosis (CS) is a common congenital defect affecting more than 1/2000 infants. Infants with CS have a premature fusion of one or multiple cranial sutures resulting in restricted brain expansion. Single gene mutations account for 15-20% of cases, largely as part of a syndrome, but the majority are nonsyndromic with complex underlying genetics. Two noncoding genomic regions contributing to CS risk were previously identified by GWAS, one near BMP2 and one within BBS9. We hypothesized that the region within BBS9 contains distal regulatory elements controlling the neighboring gene encoding BMPER, a secreted modulator of BMP signaling. To identify regulatory sequences that might underlie disease risk, we surveyed conserved noncoding sequences from both risk loci identified from the GWAS for enhancer activity in transgenic Danio rerio. We identified enhancers from both regions that direct expression to skeletal tissues, consistent with the endogenous gene expression. Importantly, for each locus, we found a skeletal enhancer that also contains a sequence variant associated with CS risk. We examined the activity of each enhancer during craniofacial development and found that the BMPER-associated enhancer is active in the restricted region of cartilage closely associated with frontal bone initiation. We used an enhanced yeast one-hybrid assay to identify transcription factor interactions with several identified enhancers, implicating multiple signaling pathways in their regulation. In a targeted screen focused on risk-associated SNPs, we further identified differential binding to alternate and reference alleles. Additionally, we found that the risk allele of the BMPER enhancer directs significantly broader expression than the reference allele in transgenic zebrafish. Our findings support a specific genetic mechanism to explain the contribution of two risk loci to CS. More broadly, our combined in vivo approach is applicable to many complex genetic diseases to build a link between association studies and specific genetic mechanisms. Author SummaryGenome-wide association studies (GWASs) provide a wealth of information implicating regions of the genome in disease risk. The great challenge is linking those regions to specific genetic mechanisms. We used complementary approaches in zebrafish and yeast to evaluate the genetic risk of craniosynostosis (CS), a craniofacial birth defect affecting 1/2000 infants where two or more skull bones are fused prematurely. Using transgenic zebrafish, we identified sequences regulating expression of two genes in the BMP signaling pathway that had been previously implicated by GWAS. These included one from each region containing a sequence variant linked to disease risk. We used an assay in cultured yeast to detect proteins binding to identified DNA sequences that could alter expression of the target genes, including changes in protein binding caused by the sequence variants. Finally, we found that transgenic fish carrying one of the variant sequences showed broader and more sustained activity throughout the skeleton. Taken together, our results support a model where variant sequences lead to increased gene expression and BMP pathway activity, contributing to aberrant skull growth in CS. Importantly, our paradigm is broadly applicable to other complex genetic diseases, potentially illuminating many connections between genome variation and disease risk.

genetics↗

bioRxiv2022

Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the smooth chorion producing a previously unknown CTB population which we term smooth-chorion-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta. Impact StatementSingle cell RNA-sequencing of distinct regions of the human placenta identifies a smooth chorion-specific cytotrophoblast population responsible for unique functions of the smooth chorion, including acting as a barrier and restricting invasion.

developmental biology↗

bioRxiv2022

Inhibiting Runx1 protects heart function after myocardial infarction

Myocardial infarction is a major cause of death worldwide. Effective treatments are required that limit adverse cardiac remodelling and preserve cardiac contractility following myocardial infarction, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile myocardium bordering a newly created infarct is functionally distinct from the remote surviving myocardium; it is also a major determinant of adverse cardiac remodelling and whole heart contractility. Expression of the transcription factor RUNX1 is increased in the border zone at 1 day after myocardial infarction, suggesting potential for targeted therapeutic intervention. Here we demonstrate that RUNX1 drives reductions in cardiomyocyte contractility, sarcoplasmic reticulum-mediated calcium release, mitochondrial density, and the expression of genes important for oxidative phosphorylation. Antagonising RUNX1 expression via short-hairpin RNA interference preserved cardiac contractile function following myocardial infarction when delivered either via direct adenoviral delivery into the border zone or via an adeno-associated virus vector administered intravenously. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with the essential co-factor CBF{beta}. Both tamoxifen-inducible Runx1-deficient and Cbf{beta}-deficient cardiomyocyte-specific mouse models demonstrated that antagonising RUNX1 function preserves the expression of genes important for oxidative phosphorylation following myocardial infarction. Our results confirm the translational potential of RUNX1 as a novel therapeutic target in myocardial infarction, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling.

pathology↗

bioRxiv2020

The genetic architecture of structural left-right asymmetry of the human brain

Left-right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and can be altered in cognitive and psychiatric disorders1-8. No mechanism has yet been identified for establishing the human brains left-right axis9. We performed multivariate genome-wide association scanning (mvGWAS) of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci affecting different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left-right axis determination in other organs of invertebrates and frogs10-12. Genetic variants affecting brain asymmetry overlapped with those influencing autism, educational attainment and schizophrenia.

neuroscience↗

bioRxiv2020

Multiscale Co-expression in the Brain

Single-cell RNA-sequencing (scRNAseq) data can reveal co-regulatory relationships between genes that may be hidden in bulk RNAseq due to cell type confounding. Using the primary motor cortex data from the Brain Initiative Cell Census Network (BICCN), we study cell type specific co-expression across 500,000 cells. Surprisingly, we find that the same gene-gene relationships that differentiate cell types are evident at finer and broader scales, suggesting a consistent multiscale regulatory landscape.

bioinformatics↗

bioRxiv2020

Amygdala-cortical control of striatal plasticity drives the acquisition of goal-directed action.

The acquisition of goal-directed action requires the encoding of specific action-outcome associations involving plasticity in the posterior dorsomedial striatum (pDMS). We first investigated the relative involvement of the major inputs to the pDMS argued to be involved in this learning-related plasticity, from prelimbic prefrontal cortex (PL) and from the basolateral amygdala (BLA). Using ex vivo optogenetic stimulation of PL or BLA terminals in pDMS, we found that goal-directed learning potentiated the PL input to direct pathway spiny projection neurons (dSPNs) bilaterally but not to indirect pathway neurons (iSPNs). In contrast, learning-related plasticity was not observed in the direct BLA-pDMS pathway. Using toxicogenetics, we ablated BLA projections to either pDMS or PL and found that only the latter was necessary for goal-directed learning. Importantly, transient inactivation of the BLA during goal-directed learning prevented the PL-pDMS potentiation of dSPNs, establishing that the BLA input to the PL is necessary for the corticostriatal plasticity underlying goal-directed learning.

neuroscience↗

bioRxiv2020

In vivo molecular signatures of cerebellar pathology in spinocerebellar ataxia type 3

BackgroundNo treatment exists for the most common dominantly inherited ataxia Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3). Successful evaluation of candidate therapeutics will be facilitated by validated noninvasive biomarkers of aspects of disease pathology recapitulated by animal models. ObjectiveWe sought to identify shared neurochemical signatures in two mouse models of SCA3 that reflect aspects of the human disease pathology. MethodsCerebellar neurochemical concentrations in homozygous YACMJD84.2 (Q84/Q84) and hemizygous CMVMJD135 (Q135) mice were measured by magnetic resonance spectroscopy at 9.4 tesla. Motivated by the shared neurochemical abnormalities in the two models, we determined the levels of neurofilament medium (NFL, indicator of neuroaxonal integrity) and myelin basic protein (MBP, indicator of myelination) in cerebellar lysates from a subset of mice and from patients with SCA3. Finally, NFL and MBP levels were measured in cerebellar extracts of Q84/Q84 mice upon sustained silencing of the mutant ATXN3 gene from 6-8 weeks-of-age until death. ResultsBoth Q84/Q84 and Q135 mice displayed lower N-acetylaspartate than wild-type littermates, indicating neuroaxonal loss/dysfunction, and lower myo-inositol and total choline, indicating disturbances in phospholipid membrane metabolism and demyelination. Cerebellar NFL and MBP levels were accordingly lower in both models as well as in the cerebellar cortex of patients with SCA3 than controls. Furthermore, long-term sustained RNAi-mediated reduction of ATXN3 levels increased NFL and MBP in Q84/Q84 cerebella. ConclusionsN-acetylaspartate, myo-inositol and total choline levels in the cerebellum are candidate biomarkers of neuroaxonal and oligodendrocyte pathology in SCA3, which are reversible by reduction of mutant ATXN3 levels.

neuroscience↗

bioRxiv2019

Single Cell Spatial Chromatin Analysis of Fixed Immunocytochemically Identified Neuronal Cells

Assays examining the open-chromatin landscape in single cells require isolation of the nucleus, resulting in the loss of spatial/microenvironment information. Here we describe CHEX-seq (CHromatin EXposed) for identifying single-stranded open-chromatin DNA regions in paraformaldehyde-fixed single cells. CHEX-seq uses light-activated DNA probes that binds to single-stranded DNA in open chromatin. In situ laser activation of the annealed probes 3-Lightning Terminator in selected cells permits the probe to act as a primer for in situ enzymatic copying of single-stranded DNA that is then sequenced. CHEX-seq is benchmarked with human K562 cells and its utility is demonstrated in dispersed primary mouse and human brain cells, and immunostained cells in mouse brain sections. Further, CHEX-seq queries the openness of mitochondrial DNA in single cells. Evaluation of an individual cells chromatin landscape in its tissue context enables \"spatial chromatin analysis\".\n\nOne Sentence SummaryA new method, CHEX-seq (CHromatin eXposed), identifies the open-chromatin landscape in single fixed cells thereby allowing spatial chromatin analysis of selected cells in complex cellular environments.

neuroscience↗

bioRxiv2018

Ontology of RNA Sequencing (ORNASEQ) and its application

BackgroundNext-generation RNA sequencing is a rapidly developing technology with complex procedures encompassing different experimental modalities. As the technology evolves and its use expand, so does the need to capture the data provenance from these sequencing studies and the need to create new tools to manage and manipulate these provenance stores.\n\nResultsHere we used the Ontology for Biomedical Investigations (OBI) and many other ontologies from the Open Biological and Biomedical Ontology (OBO) Foundry as a framework from which to create an application ontology (ORNASEQ: Ontology of RNA sequencing) to capture data provenance for next-generation RNA sequencing studies. Additionally, we provide an extensive real-life sample provenance data set for use in developing new provenance tools and additional sequencing data models.\n\nConclusionsThe Ontology of RNA Sequencing (ORNASEQ) provides core terms for use in building data models to capture the provenance from next-generation RNA sequencing studies. The supplied sample provenance data also exemplifies many of the complexities of RNA sequencing studies and underscores the need for potent workflow management systems.

genomics↗