CWLProv - Interoperable Retrospective Provenance capture and its challenges

<p>The automation of data analysis in the form of scientific workflows is a widely adopted practice in many fields of research nowadays. Computationally driven data-intensive experiments using workflows enable <strong>A</strong>utomation, <strong>S</strong>caling, <strong>A</strong>daption and <strong>P</strong>rovenance support (ASAP).</p> <p>However, there are still several challenges associated with the effective sharing, publication, understandability and reproducibility of such workflows due to the incomplete capture of provenance and the dependence on particular technical (software) platforms. This paper presents <strong>CWLProv</strong>, an approach for retrospective provenance capture utilizing open source community-driven standards involving application and customization of workflow-centric <a href="http://www.researchobject.org/">Research Objects</a> (ROs).</p> <p>The ROs are produced as an output of a workflow enactment defined in the <a href="http://www.commonwl.org/">Common Workflow Language</a> (CWL) using the CWL reference implementation and its data structures. The approach aggregates and annotates all the resources involved in the scientific investigation including inputs, outputs, workflow specification, command line tool specifications and input parameter settings. The resources are linked within the RO to enable re-enactment of an analysis without depending on external resources.</p> <p>The workflow provenance profile is represented in W3C recommended standard <a href="https://www.w3.org/TR/prov-n/">PROV-N</a> and <a href="https://www.w3.org/Submission/prov-json/">PROV-JSON</a> format to capture retrospective provenance of the workflow enactment. The workflow-centric RO produced as an output of a CWL workflow enactment is expected to be interoperable, reusable, shareable and portable across different plat-<br> forms.</p> <p>This paper describes the need and motivation for <a href="https://github.com/common-workflow-language/cwltool/tree/provenance">CWLProv</a> and the lessons learned in applying it for ROs using CWL in the bioinformatics domain.</p

Capturing interoperable reproducible workflows with Common Workflow Language

We present our ongoing work on integrating Research Object practices with Common Workflow Language, capturing and describing prospective and retrospective provenance.Accepted for talk at RO2018. Web version at http://s11.no/2018/cwl.htm

HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed in individually microdissected Globus pallidus neurons (Preliminary analysis)

We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved

Sharing interoperable workflow provenance: A review of best practices and their practical application in CWLProv

Background: The automation of data analysis in the form of scientific workflows has become a widely adopted practice in many fields of research. Computationally driven data-intensive experiments using workflows enable Automation, Scaling, Adaption and Provenance support (ASAP). However, there are still several challenges associated with the effective sharing, publication and reproducibility of such workflows due to the incomplete capture of provenance and lack of interoperability between different technical (software) platforms. Results: Based on best practice recommendations identified from literature on workflow design, sharing and publishing, we define a hierarchical provenance framework to achieve uniformity in the provenance and support comprehensive and fully re-executable workflows equipped with domain-specific information. To realise this framework, we present CWLProv, a standard-based format to represent any workflow-based computational analysis to produce workflow output artefacts that satisfy the various levels of provenance. We utilise open source community-driven standards; interoperable workflow definitions in Common Workflow Language (CWL), structured provenance representation using the W3C PROV model, and resource aggregation and sharing as workflow-centric Research Objects (RO) generated along with the final outputs of a given workflow enactment. We demonstrate the utility of this approach through a practical implementation of CWLProv and evaluation using real-life genomic workflows developed by independent groups. Conclusions: The underlying principles of the standards utilised by CWLProv enable semantically-rich and executable Research Objects that capture computational workflows with retrospective provenance such that any platform supporting CWL will be able to understand the analysis, re-use the methods for partial re-runs, or reproduce the analysis to validate the published findings.Submitted to GigaScience (GIGA-D-18-00483

Differential cell responses to nanoparticle docetaxel and small molecule docetaxel at a sub-therapeutic dose range

Current preclinical evaluations of nanoparticle taxanes have focused on the effect of nanoparticle size and shape on the efficacy and toxicity. It is generally assumed that nanoparticle therapeutics have the same cellular response on tumor and normal cells as their small molecule counterparts. Here, we show that nanoparticle taxanes can mediate cellular effects distinct from that of small molecule taxanes at the sub-therapeutic dose range. Cells that are exposed to two polymeric nanoparticle formulations of docetaxel were found to undergo a different cell cycle and cell fate than that of cells that were exposed to small molecule docetaxel. Our results suggest that nanoparticle formulation of therapeutics can affect the therapeutic effect of its cargo

Dissecting conformational contributions to glycosidase catalysis and inhibition

Glycoside hydrolases (GHs) are classified into >100 sequence-based families. These enzymes process a wide variety of complex carbohydrates with varying stereochemistry at the anomeric and other ring positions. The shapes that these sugars adopt upon binding to their cognate GHs, and the conformational changes that occur along the catalysis reaction coordinate is termed the conformational itinerary. Efforts to define the conformational itineraries of GHs have focussed upon the critical points of the reaction: substrate-bound (Michaelis), transition state, intermediate (if relevant) and product-bound. Recent approaches to defining conformational itineraries that marry X-ray crystallography of enzymes bound to ligands that mimic the critical points, along with advanced computational methods and kinetic isotope effects are discussed