Biology subjects

Martin Vingron

Publications and source records attributed to Martin Vingron.

4 recordsLinked to original sources

bioRxiv2016

ssHMM: Extracting intuitive sequence-structure motifs from high-throughput RNA-binding protein data

RNA-binding proteins (RBPs) play important roles in RNA post-transcriptional regulation and recognize target RNAs via sequence-structure motifs. To which extent RNA structure influences protein binding in the presence or absence of a sequence motif is still poorly understood. Existing RNA motif finders which produce informative motifs and simultaneously capture the relationship between primary sequence and different RNA secondary structures are missing. We developed ssHMM, an RNA motif finder that combines a hidden Markov model (HMM) with Gibbs sampling to learn the joint sequence and structure binding preferences of RBPs from high-throughput data, such as CLIP-Seq sequences, and visualizes them as a graph. Evaluations on synthetic data showed that ssHMM reliably recovers fuzzy sequence motifs in 80 to 100% of the cases. It produces motifs with higher information content than existing tools and is faster than other methods on large datasets. Examples of new sequence-structure motifs identified by ssHMM for uncharacterized RBPs are also discussed. ssHMM is freely available on Github at https://github.molgen.mpg.de/heller/ssHMM.

Bioinformatics↗

bioRxiv2016

The haplotype-resolved genome sequence of hexaploid Ipomoea batatas reveals its evolutionary history

Although the sweet potato, Ipomoea batatas, is the seventh most important crop in the world and the fourth most significant in China, its genome has not yet been sequenced. The reason, at least in part, is that the genome has proven very difficult to assemble, being hexaploid and highly polymorphic; it has a presumptive composition of two B1 and four B2 component genomes (B1B1B2B2B2B2). By using a novel haplotyping method based on de novo genome assembly, however, we have produced a half haplotype-resolved genome from [~]267Gb of paired-end sequence reads amounting to roughly 60-fold coverage. By phylogenetic tree analysis of homologous chromosomes, it was possible to estimate the time of two whole genome duplication events as occurring about 525,000 and 341,000 years ago. Our analysis also identified many clusters of genes for specialized compounds biosynthesis in this genome. This half haplotype-resolved hexaploid genome represents the first successful attempt to investigate the complexity of chromosome sequence composition directly in a polyploid genome, using direct sequencing of the polyploid organism itself rather than of any of its simplified proxy relatives. Adaptation and application of our approach should provide higher resolution in future genomic structure investigations, especially for similarly complex genomes.

Genomics↗

bioRxiv2014

Inference of interactions between chromatin modifiers and histone modifications: from ChIP-Seq data to chromatin-signaling

Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes, or are studied in vitro. Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.

Bioinformatics↗

bioRxiv2014

Epigenomic co-localization and co-evolution reveal a key role for 5hmC as a communication hub in the chromatin network of ESCs

Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC) is the most influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC colocalizes with specific interactors shows that each interaction points to chromatin remodelling, stemness, differentiation or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs.

Bioinformatics↗