bioRxiv Science⌕ Search

Biology subjects

van Helden, J.

Publications and source records attributed to van Helden, J..

5 recordsLinked to original sources

An integrated analysis tool reveals intrinsic biases in gene set enrichment

Generating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the "universe" of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.

bioinformatics↗

Motif analysis in co-expression networks reveals regulatory elements in plants: The peach as a model

Identification of functional regulatory elements encoded in plant genomes is a fundamental need to understand gene regulation. While much attention has been given to model species as Arabidopsis thaliana, little is known about regulatory motifs in other plant genera. Here, we describe an accurate bottom-up approach using the online workbench RSAT::Plants for a versatile ab-initio motif discovery taking Prunus persica as a model. These predictions rely on the construction of a co-expression network to generate modules with similar expression trends and assess the effect of increasing upstream region length on the sensitivity of motif discovery. Applying two discovery algorithms, 18 out of 45 modules were found to be enriched in motifs typical of well-known transcription factor families (bHLH, bZip, BZR, CAMTA, DOF, E2FE, AP2-ERF, Myb-like, NAC, TCP, WRKY) and a novel motif. Our results indicate that small number of input sequences and short promoter length are preferential to minimize the amount of uninformative signals in peach. The spatial distribution of TF binding sites revealed an unbalanced distribution where motifs tend to lie around the transcriptional start site region. The reliability of this approach was also benchmarked in Arabidopsis thaliana, where it recovered the expected motifs from promoters of genes containing ChIPseq peaks. Overall, this paper presents a glimpse of the peach regulatory components at genome scale and provides a general protocol that can be applied to many other species. Additionally, a RSAT Docker container was released to facilitate similar analyses on other species or to reproduce our results. One sentence summaryMotifs prediction depends on the promoter size. A proximal promoter region defined as an interval of -500 bp to +200 bp seems to be the adequate stretch to predict de novo regulatory motifs in peach

genomics↗

RSAT Var-tools: an accessible and flexible framework to predict the impact of regulatory variants on transcription factor binding

Gene regulatory regions contain short and degenerated DNA sites recognized by transcription factors (TFs). When such regions harbor SNPs, the DNA motifs where TFs bind may be affected, thereby altering the transcriptional regulation of the target genes. Such regulatory SNPs have been implicated as causal variants in GWAS studies. In this study, we describe the application of the programs Var-tools designed to predict regulatory variants, and present four case studies to illustrate their usage and applications. In brief, Var-tools facilitate i) obtaining variation information, ii) interconversion of variation file formats, iii) retrieval of sequences surrounding variants, and iv) calculating the change on predicted TF affinity scores between alleles, using motif scanning approaches. Notably, the tools support the analysis of haplotypes. The tools are included within the well-maintained suite Regulatory Sequence Analysis Tools (RSAT, http://rsat.eu), and accessible through a web interface that currently enables analysis of five metazoa and ten plant genomes. Vart-tools can also be used in command-line with any locally-installed Ensembl genome. Users can input personal collections of variants and motifs, providing flexibility in the analysis.

bioinformatics↗

SnakeChunks: modular blocks to build Snakemakeworkflows for reproducible NGS analyses

SummaryNext-Generation Sequencing (NGS) is becoming a routine approach for most domains of life sciences, yet there is a crucial need to improve the automation of processing for the huge amounts of data generated and to ensure reproducible results. We present SnakeChunks, a collection of Snakemake rules enabling to compose modular and user-configurable workflows, and show its usage with analyses of transcriptome (RNA-seq) and genome-wide location (ChIP-seq) data.\n\nAvailabilityThe code is freely available (github.com/SnakeChunks/SnakeChunks), and documented with tutorials and illustrative demos (snakechunks.readthedocs.io).\n\nContactclaire.rioualen@inserm.fr, jacques.van-helden@univ-amu.fr\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

Sequanix: A Dynamic Graphical Interface for Snakemake Workflows

SummaryWe designed a PyQt graphical user interface - Sequanix - aiming at democratizing the use of Snakemake pipelines. Although the primary goal of Sequanix was to facilitate the execution of NGS Snakemake pipelines available in the Sequana project (http://sequana.readthedocs.io), it can also handle any Snakemake pipelines. Therefore, Sequanix should be useful to all Snakemake developers willing to expose their pipelines to a wider audience.\n\nAvailabilitySource code available on http://github.com/sequana/sequana and standalone on http://bioconda.github.io (sequana package).

bioinformatics↗