Integration of Data in Pathogenomics: Three Layers of cellular complexity and an XML-based Framework

Summary Integration of data in pathogenomics is achieved here considering three different levels of cellular complexity: (i) genome and comparative genomics, (ii) enzyme cascades and pathway analysis, (iii) networks including metabolic network analysis.After direct sequence annotation exploiting tools for protein domain annotation (e.g. AnDOM) and analysis of regulatory elements (e.g. the RNA analyzer tool) the analysis results from extensive comparative genomics are integrated for the first level, pathway alignment adds data for the pathway level, elementary mode analysis and metabolite databanks add to the third level of cellular complexity. For efficient data integration of all data the XML based platform myBSMLStudio2003 is discussed and developed here. It integrates XQuery capabilities, automatic scripting updates for sequence annotation and a JESS expert system shell for functional annotation. In the context of genome annotation platforms in place (GenDB, PEDANT) these different tools and approaches presented here allow improved functional genome annotation as well as data integration in pathogenomics.

Download Full-text

Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis

10.1101/2021.09.16.460328 ◽

2021 ◽

Author(s):

Dennis A Sun ◽

Nipam H Patel

Keyword(s):

Gene Expression ◽

Genome Annotation ◽

Time Course ◽

Regulatory Elements ◽

Rna Seq ◽

Genome Wide ◽

Long Read ◽

Amphipod Crustacean ◽

Accessible Chromatin

AbstractEmerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of novel data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We leverage a variety of bioinformatic tools to discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms.Primary Findings-Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis-Combined short- and long-read RNA-Seq improves the Parhyale genome annotation-ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements-NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding-Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics-Integration of accessibility and gene expression reveals possible enhancers and repressors-Omni-ATAC can identify known and novel regulatory elements

Download Full-text