bioRxiv Science⌕ Search

Biology subjects

Maurya, M. R.

Publications and source records attributed to Maurya, M. R..

4 recordsLinked to original sources

The CFDE Workbench: Integrating Metadata and Processed Data from Common Fund Programs

The NIH Common Fund Data Ecosystem (CFDE) program was established to facilitate data accessibility and interoperability across multiple Common Fund (CF) programs and promote collaborations and new discoveries by combining data from different CF programs. The CFDE Data Resource Center (DRC) was tasked with developing two web-based portals: an Information Portal to serve information about the CFDE, and a Data Portal to host harmonized metadata and processed data contributed by participating CF Data Coordination Centers (DCCs) and other sources. To achieve these goals, the CFDE DRC developed the CFDE Workbench, a web-based platform that hosts highly processed data, metadata, tools, use cases, and analyses developed by the CFDE. The Crosscut Metadata Model (C2M2) and several other processed data formats are hosted by the CFDE Workbench, including set libraries (XMTs), Knowledge Graph (KG) assertions, and attribute tables. These processed data formats make information derived from CF programs more findable, accessible, interoperable, and reusable (FAIR) and artificial intelligence (AI)-ready for cross-DCC knowledge discovery. In addition to these processed data formats, several other assets are served by the Workbench, including Extract Transform Load (ETL) pipelines, OpenAPI-documented and SmartAPI-registered Representational State Transfer (REST) Application Programming Interfaces (APIs), entity pages such as gene, drug, disease, or tissue landing pages, Playbook Workflow Builder (PWB) metanodes which are codified workflow steps involving DCC APIs, and chatbot specifications which are prompts helping chatbots to use DCC APIs to answer a wide range of user queries. Besides serving data, metadata, and code assets, the CFDE Workbench also has several tools that use these data, metadata, and code assets to enable cross-CF-program knowledge discovery use cases. Overall, the CFDE Workbench is a platform that consolidates efforts toward making CF programs funded resources harmonized, FAIR, and AI-ready. The CFDE Workbench website is available from: https://cfde.info/.

bioinformatics↗

Playbook Workflow Builder: Interactive Construction of Bioinformatics Workflows from a Network of Microservices

Many biomedical research projects produce large-scale datasets that may serve as resources for the research community for hypothesis generation, facilitating diverse use cases. Towards the goal of developing infrastructure to support the findability, accessibility, interoperability, and reusability (FAIR) of biomedical digital objects and maximally extracting knowledge from data, complex queries that span across data and tools from multiple resources are currently not easily possible. By utilizing existing FAIR application programming interfaces (APIs) that serve knowledge from many repositories and bioinformatics tools, different types of complex queries and workflows can be created by using these APIs together. The Playbook Workflow Builder (PWB) is a web-based platform that facilitates interactive construction of workflows by enabling users to utilize an ever-growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem. Via a user-friendly web-based user interface (UI), workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflows are provided in reports containing textual descriptions, as well as interactive and downloadable figures and tables. To demonstrate the ability of the PWB to generate meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases sieves novel targets for individual cancer patients using data from the GTEx, LINCS, Metabolomics, GlyGen, and the ExRNA Communication Consortium (ERCC) Common Fund (CF) Data Coordination Centers (DCCs). The workflows created with the PWB can be published and repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/.

bioinformatics↗

Modeling transcriptional regulation of the cell cycle using a novel cybernetic-inspired approach

Quantitative understanding of cellular processes, such as cell cycle and differentiation, is impeded by various forms of complexity ranging from myriad molecular players and their multilevel regulatory interactions, cellular evolution with multiple intermediate stages, lack of elucidation of cause-effect relationships among the many system players, and the computational complexity associated with the profusion of variables and parameters. In this paper, we present an elegant modeling framework based on the cybernetic concept that biological regulation is inspired by objectives embedding entirely novel strategies for dimension reduction, process stage specification through the system dynamics, and innovative causal association of regulatory events with the ability to predict the evolution of the dynamical system. The elementary step of the modeling strategy involves stage-specific objective functions that are computationally-determined from experiments, augmented with dynamical network computations involving end point objective functions, mutual information, change point detection, and maximal clique centrality. We demonstrate the power of the method through application to the mammalian cell cycle, which involves thousands of biomolecules engaged in signaling, transcription, and regulation. Starting with a fine-grained transcriptional description obtained from RNA sequencing measurements, we develop an initial model, which is then dynamically modeled using the cybernetic-inspired method (CIM), utilizing the strategies described above. The CIM is able to distill the most significant interactions from a multitude of possibilities. In addition to capturing the complexity of regulatory processes in a mechanistically causal and stage-specific manner, we identify the functional network modules, including novel cell cycle stages. Our model is able to predict future cell cycles consistent with experimental measurements. We posit that this state-of-the-art framework has the promise to extend to the dynamics of other biological processes, with a potential to provide novel mechanistic insights. STATEMENT OF SIGNIFICANCECellular processes like cell cycle are overly complex, involving multiple players interacting at multiple levels, and explicit modeling of such systems is challenging. The availability of longitudinal RNA measurements provides an opportunity to "reverse-engineer" for novel regulatory models. We develop a novel framework, inspired using goal-oriented cybernetic model, to implicitly model transcriptional regulation by constraining the system using inferred temporal goals. A preliminary causal network based on information-theory is used as a starting point, and our framework is used to distill the network to temporally-based networks containing essential molecular players. The strength of this approach is its ability to dynamically model the RNA temporal measurements. The approach developed paves the way for inferring regulatory processes in many complex cellular processes.

systems biology↗

MetENP/MetENPWeb: An R package and web application for metabolomics enrichment and pathway analysis in Metabolomics Workbench

With the advent of high throughput mass spectrometric methods, metabolomics has emerged as an essential area of research in biomedicine with the potential to provide deep biological insights into normal and diseased functions in physiology. However, to achieve the potential offered by metabolomics measures, there is a need for biologist-friendly integrative analysis tools that can transform data into mechanisms that relate to phenotypes. Here, we describe MetENP, an R package, and a user-friendly web application deployed at the Metabolomics Workbench site extending the metabolomics enrichment analysis to include species-specific pathway analysis, pathway enrichment scores, gene-enzyme information, and enzymatic activities of the significantly altered metabolites. MetENP provides a highly customizable workflow through various user-specified options and includes support for all metabolite species with available KEGG pathways. MetENPweb is a web application for calculating metabolite and pathway enrichment analysis. Availability and ImplementationThe MetENP package is freely available from Metabolomics Workbench GitHub: (https://github.com/metabolomicsworkbench/MetENP), the web application, is freely available at (https://www.metabolomicsworkbench.org/data/analyze.php)

bioinformatics↗