Biology subjects

Hayes, A.

Publications and source records attributed to Hayes, A..

17 recordsLinked to original sources

bioRxiv2026

SELECT 2.0: Refined and open access SELection Endpoints in Communities of bacTeria (SELECT) method to determine concentrations of antibiotics that may select for antimicrobial resistance in the environment

Antimicrobial resistance (AMR) is a significant and growing threat to human, plant and animal health, the global economy, and food security. The One Health approach to AMR recognises the role of the environment in the evolution, emergence, and dissemination of AMR. In part, this is due to anthropogenic pollution that releases AMR organisms alongside cocktails of compounds that may select for AMR in situ, which then pose an exposure risk to humans and animals. This has spurred growing interest from cross-sectoral stakeholders in environmental risk assessment (ERA) of antibiotics, with regards to their selective potential. Many different experimental and modelling approaches have been used to determine the lowest concentration of an antibiotic that may select for AMR. Debates continue regarding which individual approach, if any, may be best for determining concentrations of antibiotics that may select for AMR, for ERA purposes. This paper contributes to this ongoing discourse by refining and using a previously published method SELECT (SELection Endpoints in Communities of bacTeria) to rapidly generate predicted no effect concentrations for resistance (PNECRs) for 32 antibiotics on the premise that reduction in growth of complex community of bacteria correlates with selection for AMR resistance genes. The database of PNECRs of antibiotics presented here is the largest generated using a single experimental, empirical approach that will aid future efforts towards creating a standardised test. PNECR data were used to conduct ERAs using measured environmental concentrations of antibiotics to rank antibiotics by potential selection risk in different environments. The experimental approach and statistical code have been made open access, with online tutorials available to facilitate other laboratories using the SELECT 2.0 method. Finally, we discuss the limitations of this approach and how these could be addressed in future studies.

microbiology↗

bioRxiv2026

Endocrine-metabolic decoupling drives stress vulnerability in dystrophin deficiency

Skeletal muscle orchestrates systemic metabolism, dynamically coordinating glucose uptake and fuel use to match energy demand. In Duchenne muscular dystrophy, loss of dystrophin is associated with altered metabolic regulation. In the mdx mouse, we show that physiological stress reveals impaired coordination between insulin and stress responses: glucocorticoid signalling increases without a proportional rise in insulin secretion, resulting in systemic hyperglycaemia despite preserved capacity for muscle glucose uptake. These data support a multi-tissue dystrophinopathy associated with altered endocrine-metabolic coordination. Skeletal muscle glycogen is elevated and incompletely mobilised under stress. The heart maintains high glucose uptake, whereas the brain exhibits reduced uptake, highlighting tissue specific differences in metabolic response. Acute insulin supplementation improves systemic glucose control and restores stress-induced behavioural deficits. Likewise, empagliflozin-mediated glucose offloading reduces stress-associated blood glucose spikes and is associated with improved muscle function to levels comparable with standard care prednisolone. These findings identify impaired coordination of endocrine and metabolic responses during stress as a contributor to metabolic vulnerability in DMD and suggest that modulating insulin availability or glucose flux can improve systemic metabolic control.

systems biology↗

bioRxiv2025

Simple sequence repeats power Staphylococcus aureus adaptation

Understanding Staphylococcus aureus adaptation is foundational for addressing the challenges posed by this pathogen. Using evolutionary convergence analysis on 7099 S. aureus genomes we uncovered frequent, reversible loss-of-function (LoF) mutations caused by simple sequence repeats (SSRs). Functional assays showed SSRs are potent, length-dependent switches that activate and deactivate genes, a mechanism exemplified by frequent LoF mutations in mutL (DNA mismatch repair) that causes a hypermutator phenotype. Analysis of over 600 episodes of human S. aureus colonisation and infection confirmed laboratory findings and showed that mutL SSR hypermutability behaves like a phase-variable evolutionary capacitor that unlocks subsequent adaptive SSR variations. We also experimentally demonstrate that SSRs facilitate foreign DNA uptake (hsdR restriction endonuclease) and lead to gentamicin-resistant small colony variants that are known to cause persistent infections (menF menadione biosynthesis). Furthermore, the phenomenon is widespread, with 27 of 29 diverse human microbiome samples harbouring S. aureus with distinct SSR subpopulations, indicative of niche-specific adaptations. Thus, SSRs are potent reservoirs of previously unrecognized S. aureus genetic heterogeneity that confer rapid adaptive capacity, including in antigens targeted by past vaccine trials. A deeper understanding of SSR evolutionary trajectories has the potential to improve treatments and to anticipate S. aureus responses to new therapies.

microbiology↗

bioRxiv2025

Common non-antibiotic drugs enhance selection for antimicrobial resistance in mixture with ciprofloxacin

Antimicrobial resistance (AMR) is a major health concern, and a range of antibiotic and non-antibiotic agents can select for AMR across a range of concentrations. Selection for AMR is often investigated using single compounds, however, in the natural environment and the human body, pharmaceuticals will be present as mixtures, including both non-antibiotic drugs (NADs), and antibiotics. Here, we assessed the effects of one of three NADs in combination with ciprofloxacin, a commonly used antibiotic that is often found at concentrations in global freshwaters sufficiently high to select for AMR. We used a combination of growth assays and qPCR to determine selective concentrations of mixtures and used metagenome sequencing to identify changes to the resistome and community composition. The selective concentration of ciprofloxacin was reduced from 40{micro}g/L to 10{micro}g/L in the mixtures, and mixtures showed a stronger selection for some AMR genes such as tolC and qnrB. The communities exposed to the mixtures also showed changed community compositions. These results demonstrate that NADs and ciprofloxacin are more selective than ciprofloxacin alone, and these mixtures can cause distinct changes to the community composition. This indicates that future work should consider combinations of antibiotics and NADs as drivers of AMR when considering its maintenance and acquisition.

microbiology↗

bioRxiv2024

Advancements in Inflammation Parallels Myopenia in Winnie Mice Model of Spontaneous Chronic Colitis

BackgroundInflammatory bowel disease (IBD) is characterized by gastrointestinal inflammation and systemic complications, including muscle wasting. Musculoskeletal conditions have remained an unappreciated aspect of IBD. This study aimed to describe the Winnie mouse models skeletal muscle phenotype and functional alterations. This model spontaneously develops chronic colitis that closely resembles human IBD. MethodsWinnie mice and C57BL/6 (littermate) controls were evaluated at 5-6 weeks (pre-colitis) and 15-16 weeks (active colitis). Assessments included disease activity, inflammation, muscle function tests, and ex vivo analyses of the soleus (SOL) and tibialis anterior (TA) muscles for mass and histology. ResultsAt 5-6 weeks, Winnie mice showed no disease activity or muscle changes. At 15 weeks, Winnie mice exhibited significantly higher disease activity index (DAI) and elevated lipocalin-2 (LCN-2) levels than controls. SOL and TA muscles showed decreased weights and fibre sizes, which correlated significantly with LCN-2 levels. Wheel-running activity was reduced, which correlated with increased LCN-2 levels and DAI. DAI negatively correlated with muscle mass and fibre size. Grip strength remained unaltered despite these changes. ConclusionThe Winnie mouse model develops significant skeletal muscle alterations paralleling intestinal inflammation progression, characterized by reduced muscle mass and size with preserved strength but impaired functional endurance capacity. These findings establish the Winnie model as a valuable tool for investigating IBD-associated muscle wasting. Key Messages1. What is already known? O_LIInflammatory bowel disease (IBD) is associated with systemic complications, including muscle dysfunction. C_LI 2. What is new here? O_LIThe Winnie mouse model of chronic colitis develops skeletal muscle alterations that correlate with the progression of intestinal inflammation. C_LIO_LIMuscle changes in Winnie mice include reduced muscle mass, decreased fibre size, and, functional decline but preserved grip strength. C_LI 3. How can this study help patient care? O_LIThis research highlights the importance of monitoring muscle health in IBD patients and suggests potential targets for interventions to preserve muscle function. C_LIO_LIThe Winnie model provides a valuable tool for testing therapies aimed at addressing muscle dysfunction in IBD. C_LI

physiology↗

bioRxiv2024

Horizontal transfer of nuclear DNA in transmissible cancer

Although somatic cell genomes are usually entirely clonally inherited, nuclear DNA exchange between cells of an organism can occur sporadically by cell fusion, phagocytosis or other mechanisms1-3. This phenomenon has long been noted in the context of cancer, where it could be envisaged that DNA horizontal transfer plays a functional role in disease evolution4-13. However, an understanding of the frequency and significance of this process in naturally occurring tumours is lacking. The host-tumour genetic discordance of transmissible cancers, malignant clones which pass between animals as allogeneic grafts, provides an opportunity to investigate this. We screened for host-to-tumour horizontal transfer of nuclear DNA in 174 tumours from three transmissible cancers affecting dogs and Tasmanian devils, and detected a single instance in the canine transmissible venereal tumour (CTVT). This involved introduction of a 15-megabase dicentric genetic element, composed of 11 rearranged fragments of six chromosomes, to a CTVT sublineage occurring in Asia around 2,000 years ago. The element forms the short arm of a small submetacentric chromosome, and derives from a dog with ancestry associated with the ancient Middle East. The introduced DNA fragment is transcriptionally active and has adopted the expression profile of CTVT. Its 143 genes do not, however, confer any obvious advantage to its spatially restricted CTVT sublineage. Our findings indicate that nuclear DNA horizontal transfer, although likely a rare event in tumour evolution, provides a viable mechanism for the acquisition of genetic material in naturally occurring cancer genomes.

cancer biology↗

bioRxiv2024

In dystrophic mdx hindlimb muscles where fibrosis is limited versican haploinsufficiency transiently improves contractile function without decreasing inflammation

The provisional matrix protein versican is upregulated in Duchenne muscular dystrophy. Versican heightens inflammation in fibrotic diseases and is involved in myogenesis. In fibrotic diaphragm muscles from dystrophic mdx mice, versican reduction attenuated macrophage infiltration and improved contractile function. We investigated the association between versican and mdx hindlimb muscle pathology, where inflammation and regeneration are increased but fibrosis is minimal. Immunohistochemistry and qRT-PCR were used to assess how fiber type and glucocorticoids (-methylprednisolone) modulate versican expression. Female mdx and male versican haploinsufficient (hdf) mice were bred resulting in male mdx-hdf and mdx (control) pups. Versican expression, contractile function, and pathology were evaluated in fast extensor digitorum longus (EDL) and slow soleus muscles, excised under medetomidine-midazolam- fentanyl anesthesia. Versican immunoreactivity was highest in soleus muscles. Versican mRNA transcripts were reduced by -methylprednisolone in soleus, but not EDL, muscles. Versican expression was decreased in soleus muscles from 6-week-old mdx-hdf mice leading to increased force output and a modest reduction in fatiguability. These functional benefits were not accompanied by decreased inflammation; muscle architecture, regeneration markers, and fiber type also did not differ between genotypes. Improvements in soleus function were lost in adult (20-week-old) mdx-hdf mice with no significant effect of versican haploinsufficiency on macrophage infiltration and regeneration markers. Soleus muscles from juvenile mdx mice were most responsive to pharmacological or genetic approaches targeting versican; however, the benefits of versican reduction were limited due to low fibrosis. Pre-clinical matrix research in dystrophy should account for muscle phenotype and the interdependence between the fibrosis and inflammation. NEW & NOTEWORTHYThe proteoglycan versican is upregulated in muscular dystrophy. In fibrotic diaphragm muscles from mdx mice, versican reduction attenuated macrophage infiltration and improved performance. Here, in hindlimb muscles from 6- and 20-week-old mdx mice, where pathology is mild, versican reduction did not decrease inflammation and contractile function improvements were limited to juvenile mice. In dystrophic mdx muscles, the association between versican and inflammation is mediated by fibrosis, demonstrating interdependence between the immune system and extracellular matrix.

physiology↗

bioRxiv2024

Antimicrobial effects, and selection for AMR by non-antibiotic drugs on bacterial communities

Antimicrobial resistance (AMR) is a major threat to human, veterinary, and agricultural health. AMR can be directly selected for by antibiotics, and indirectly co-selected for by biocides and metals. Some evidence suggests that non-antibiotic drugs (NADs) can co-select for AMR, but previous work focused on exposing single model bacterial species to predominately high concentrations of NADs. Here, we determined the antimicrobial effect and selective potential of three commonly used NADs against a complex bacterial community using a combination of culture based, metagenomic, and metratranscriptomic approaches. We found that three of five NADs tested on growth significantly reduced growth of a bacterial community, although only one (17-{beta}-estradiol) selected for an AMR marker using qPCR. Whole metagenome sequencing indicated that there was no clear strong selection by NADs for antibiotic resistance genes, nor effects on community composition. However, some changes in relative abundance of metal resistance genes were observed after exposure to diclofenac, metformin, and 17-{beta}-estradiol. Together, these results indicate that the NADs tested likely do not strongly select for AMR at both clinically and environmentally relevant concentrations.

microbiology↗

bioRxiv2024

Dietary methionine/choline deficiency affects behavioural and molecular circadian rhythms

The feeding/fasting cycles controlled by our circadian clock impose great daily metabolic and physiological changes, and yet investigations into the consequences of metabolic deficiencies, either dietary or genetic, have often ignored the time of day or the circadian time of the animals or subjects. In addition, these deficiencies may themselves disrupt our circadian clock, causing secondary metabolic, physiological and behavioural disorders. Dietary methionine/choline deficiency in rodents is a common model for human non-alcoholic steatohepatitis, but methionine and choline are nutrients essential for many other processes beyond fatty acid synthesis in the liver, including biological methylations and 1-carbon metabolism, regulation of translation notably via the mTOR pathway, phospholipid synthesis, polyamine pathway and glutathione synthesis. We have previously shown that circadian rhythms in many organisms are highly sensitive to deficiency or excesses of 1-carbon metabolites. Using a methionine/choline deficient diet in mice, we illustrate the nutrigenomic crosstalk between circadian rhythms and 1-carbon metabolism. We show not only that circadian locomotor activity behaviour is profoundly, rapidly and reversibly affected by methionine/choline deficiency, but also that the effects of methionine/choline deficiency on gene expression and 1-carbon metabolites are dependent on circadian time, illustrating the importance of considering circadian rhythms in metabolic studies. This study also highlights the impact of what we eat, or dont, on our behaviour and biological rhythms.

physiology↗

bioRxiv2023

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features

Extension of prostate cancer beyond the primary site into the surrounding organs by local invasion or nodal metastasis is associated with poor prognosis. The emergence and evolution of cancer clones at this early stage of expansion and spread has not been studied in detail. We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes. Based on these data, we delineated the route of tumour progression and metastasis following the transformation of adenocarcinoma to amphicrine morphology, the molecular events leading to whole genome duplication associated with a single clonal expansion and identified putative driver events associated with local invasion and lymph node metastasis. We also correlated genomic changes associated with differences in morphology and identified putative driver events associated with spread to seminal vesicle invasion and lymph node metastasis. Taken together, these findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes associated with morphological transformation. Our results demonstrate the value of integrating multi-region sequencing with histopathological data to study tumour evolution and identify mechanisms of prostate cancer spread.

cancer biology↗

bioRxiv2021

Antibody response patterns to Helicobacter pylori infection in a rural Ugandan population cohort.

BackgroundHelicobacter pylori (H. pylori) establishes life-long infection in humans in the absence of treatment and has been associated with a variety of gastrointestinal conditions including peptic ulcer and gastric cancer. Antibody responses to H. pylori antigens are found to be associated with disease risk, however, data from Africa are scarce. MethodsTo assess the seroprevalence of H. pylori and characterise antibody response patterns, we measured serum IgG antibody levels to 14 antigens among 7,211 individuals in a rural Ugandan population cohort. Multivariate-adjusted linear regression models were fitted to investigate the influence of age, sex, and co-infection on antibody seroreactivity levels. ResultsH. pylori seroprevalence was 95% in our study population, with 94% of individuals seropositive in childhood (<15 years). In H. pylori positive individuals, we found a markedly high seroprevalence (~99%) and antibody levels to the high-risk antigens CagA and VacA, in addition to Cag{delta}. HSV-2 co-infection was significantly associated with higher IgG levels of CagA and VacA (OR=1.10, 95% C. I=1.05-1.16). HIV infection was associated with lowered IgG levels to CagA (OR=0.86, 95% C.I.=0.80-0.93), and HPV infection was associated with increased IgG levels to VacA (OR=1.16, 95% C.I.=1.11-1.21). ConclusionsH. pylori in this population is ubiquitous from childhood, with a high prevalence and high seroreactivity levels of high-risk antigens, suggesting chronic active inflammatory responses in individuals that are indicative of risk of disease. Further investigation is warranted to fully understand the relationship between host, immunogenicity, and clinical outcomes to better stratify by risk and improve treatment. Key MessagesO_LIAntibody responses to H. pylori antigens are found to be associated with risk of gastric cancer, however, despite the high seroprevalence in African populations, data from Africa are scarce. This is the first study of antibody response patterns and their determinants from an African population. C_LIO_LIOur study shows a population where H. pylori is ubiquitous from childhood, and seroprevalence of virulent antigens is distinctively high suggesting an increased of disease compared to other populations. C_LIO_LIWe observe inter-individual variation in virulent antibody responses partly influenced by co-infection. C_LIO_LIWe highlight crucial insights into antibody-based biomarkers of disease risk and reinforce the need for population-based H. pylori screening and treatment programmes for gastric cancer control. C_LI

immunology↗

bioRxiv2020

Cell-type, single-cell, and spatial signatures of brain-region specific splicing in postnatal development

Alternative RNA splicing varies across brain regions, but the single-cell resolution of such regional variation is unknown. Here we present the first single-cell investigation of differential isoform expression (DIE) between brain regions, by performing single cell long-read transcriptome sequencing in the mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 (www.isoformAtlas.com). Using isoform tests for brain-region specific DIE, which outperform exon-based tests, we detect hundreds of brain-region specific DIE events traceable to specific cell-types. Many DIE events correspond to functionally distinct protein isoforms, some with just a 6-nucleotide exon variant. In most instances, one cell type is responsible for brain-region specific DIE. Cell types indigenous to only one anatomic structure display distinctive DIE, where for example, the choroid plexus epithelium manifest unique transcription start sites. However, for some genes, multiple cell-types are responsible for DIE in bulk data, indicating that regional identity can, although less frequently, override cell-type specificity. We validated our findings with spatial transcriptomics and long-read sequencing, yielding the first spatially resolved splicing map in the postnatal mouse brain (www.isoformAtlas.com). Our methods are highly generalizable. They provide a robust means of quantifying isoform expression with cell-type and spatial resolution, and reveal how the brain integrates molecular and cellular complexity to serve function.

neuroscience↗

bioRxiv2020

Restricted sequence variation in Streptococcus pyogenes penicillin binding proteins

A recent clinical report has linked Streptococcus pyogenes {beta}-lactam antibiotic resistance to mutations in the Penicillin Binding Protein PBP2x. To determine whether this is an isolated case or reflects a broader prevalence of mutations that might confer reduced {beta}-lactam susceptibility, we investigated the relative frequency of penicillin binding protein (PBP) sequence variation within a global database of 9,667 S. pyogenes isolates. We found that mutations in S. pyogenes PBPs (PBP2x, PBP1a, PBP1b and PBP2a) occur infrequently across this global database with less than 3 amino acid changes differing between >99% of the global population. Only 4 of the 9,667 strains contained mutations near transpeptidase active sites. The reported PBP2x T553K substitution was not identified. These findings are in contrast to those of 2,520 S. pneumococcus sequences where PBP mutations are relatively frequent and are often located in key {beta}-lactam binding pockets. These data, combined with the general lack of penicillin resistance reported in S. pyogenes worldwide, suggests that extensive, unknown, constraints restrict S. pyogenes PBP sequence plasticity. These findings imply that while heavy antibiotic pressure may select for mutations in the PBPs, there is currently no evidence of such mutations becoming fixed in the S. pyogenes population nor that mutations are being sequentially acquired in the PBPs. ImportancePenicillin is the first line therapeutic option for Streptococcus pyogenes infections. Despite the global high prevalence of S. pyogenes infections and widespread use of penicillin, reports of resistance to penicillin have been incredibly rare. Recently, penicillin resistance was detected in two clinical S. pyogenes isolates with accompanying mutations in the active site of the penicillin binding protein PBP2x, raising concerns that penicillin resistance may become more widespread. We screened a global database of S. pyogenes genome sequences to investigate the frequency of penicillin binding protein (PBP) mutations, identifying that PBP mutations are uncommon relative to Streptococcus pneumoniae. These findings support clinical observations that penicillin resistance is rare in S. pyogenes, and suggest that there are considerable constraints on S. pyogenes PBP sequence variation.

microbiology↗

bioRxiv2019

Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases

Deregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer yet inhibitors against these kinases currently show use in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and what may undermine such dependency is poorly understood. Here we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2-activation, involving as a critical mechanistic events loss of the CDK inhibitor p21CIP1 and gain of its regulator, the ubiquitin ligase subunit SKP2. Combined inhibition of MET/FAK and CDK4/6 eliminates proliferation capacity of cancer cells in culture, and enhances tumour growth inhibition in vivo. Activation of the MET/FAK axis is known to arise through cancer extrinsic and intrinsic cues. Our work predicts that such cues support cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases and identifies MET/FAK as a tractable route to broaden the utility of CDK4/6 inhibitor-based therapies in the clinic.

cancer biology↗

bioRxiv2017

Reconciling age-related changes in behavioural and neural indices of human perceptual decision making

Ageing impacts on decision making behaviour across a wide range of cognitive tasks and scenarios. Computational modeling has proven highly valuable in providing mechanistic interpretations of these age-related differences; however, the extent to which model parameter differences accurately reflect changes to the underlying neural computations has yet to be tested. Here, we measured neural signatures of decision formation as younger and older participants performed motion discrimination and contrast-change detection tasks, and compared the dynamics of these signals to key parameter estimates from fits of a prominent accumulation-to-bound model (drift diffusion) to behavioural data. Our results indicate marked discrepancies between the age-related effects observed in the model output and the neural data. Most notably, while the model predicted a higher decision boundary in older age for both tasks, the neural data indicated no such differences. To reconcile the model and neural findings, we used our neurophysiological observations as a guide to constrain and adapt the model parameters. In addition to providing better fits to behaviour on both tasks, the resultant neurally-informed models furnished novel predictions regarding other features of the neural data which were empirically validated. These included a slower mean rate of evidence accumulation amongst older adults during motion discrimination and a beneficial reduction in between-trial variability in accumulation rates on the contrast-change detection task, which was linked to more consistent attentional engagement. Our findings serve to highlight how combining human brain signal measurements with computational modelling can yield unique insights into group differences in neural mechanisms for decision making.

neuroscience↗

bioRxiv2017

Classifying cells with Scasat - a tool to analyse single-cell ATAC-seq

MotivationThe assay for transposase-accessible chromatin using sequencing (ATAC-seq) reveals the landscape and principles of DNA regulatory mechanisms by identifying the accessible genome of mammalian cells. When done at single-cell resolution, it provides an insight into the cell-to-cell variability that emerges from identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells. Processing of single-cell ATAC-seq requires a number of steps and a simple pipeline to processes and analyse single-cell ATAC-seq is not yet available.\n\nResultsThis paper presents ScAsAT (single-cell ATAC-seq analysis tool), a complete pipeline to process scATAC-seq data with simple steps. The pipeline is developed in a Jupyter notebook environment that holds the executable code along with the necessary description and results. For the initial sequence processing steps, the pipeline uses a number of well-known tools which it executes from a python environment for each of the fastq files. While functions for the data analysis part are mostly written in R, it is robust, flexible, interactive and easy to extend. The pipeline was applied to a single-cell ATAC-seq dataset in order to identify different cell-types from a complex cell mixture. The results from Scasat showed that open chromatin location corresponding to potential regulatory elements can account for cellular heterogeneity and can identify regulatory regions that separates cells from a complex population.\n\nAvailabilityThe jupyter notebook with the complete pipeline applied to the dataset published with this paper are publicly available on the Github (https://github.com/ManchesterBioinference/Scasat). An additional notebook is also provided for analysis of a publicly available dataset. The fastq files are submitted at ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-6116.\n\nContactsyed.murtuzabaker@manchester.ac.uk and magnus.rattray@manchester.ac.uk\n\nSupplementary informationSupplementary data are available at bioRxiv online.

bioinformatics↗

bioRxiv2017

Enabling Precision Medicine via standard communication of NGS provenance, analysis, and results

A personalized approach based on a patients or pathogens unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to FAIR guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet lab procedures to computational methods. The BioCompute framework (https://osf.io/zm97b/) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCO) offer that standard, and are freely accessible as a GitHub organization (https://github.com/biocompute-objects) following the \"Open-Stand.org principles for collaborative open standards development\". By communication of high-throughput sequencing studies using a BCO, regulatory agencies (e.g., FDA), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next generation sequencing workflow exchange, reporting, and regulatory reviews.

scientific communication and education↗