Biology subjects

Laros, J. F. J.

Publications and source records attributed to Laros, J. F. J..

3 recordsLinked to original sources

bioRxiv2020

Mutalyzer 2: Next Generation HGVS Nomenclature Checker

Unambiguous variant descriptions are of utmost importance in clinical genetic diagnostics, scientific literature, and genetic databases. The Human Genome Variation Society (HGVS) publishes a comprehensive set of guidelines on how variants should be correctly and unambiguously described. We present the implementation of the Mutalyzer 2 tool suite, designed to automatically apply the HGVS guidelines so users do not have to deal with the HGVS intricacies explicitly to check and correct their variant descriptions. Mutalyzer is profusely used by the community, having processed over 133 million descriptions since its launch. Over a five year period, Mutalyzer reported a correct input in approximately 50% of cases. In 41% of the cases either a syntactic or semantic error was identified and for approximately 7% of cases, Mutalyzer was able to automatically correct the description.

bioinformatics↗

bioRxiv2019

Zbtb24 binding protects promoter activity by antagonizing DNA methylation in mESCs

DNA methylation is a key epigenetic modification essential for normal development. How particular factors control DNA methylation patterns and activity of a given locus is incompletely understood. The zinc finger protein Zbtb24 has been implicated in transcriptional activation/repression and the DNA methylation maintenance pathway. Here, using whole genome bisulfite sequencing in mouse embryonic stem cells, we report that besides a general trend towards DNA hypomethylation, many genomic sites gain methylation in the absence of Zbtb24 and they include promoters of actively transcribed genes. DNA hypomethylation is not generally associated with gene expression changes, suggesting that additional epigenetic safeguards are in place that ensure silencing of the affected loci. Remarkably, we identify a set of genes that is particularly susceptible to Zbtb24 occupancy. At these sites, Zbtb24 binding is not only required for gene activity but also required for maintaining the unmethylated state of the promoter.

molecular biology↗

bioRxiv2019

Reference-free resolution of long-read metagenomic data

BackgroundRead binning is a key step in proper and accurate analysis of metagenomics data. Typically, this is performed by comparing metagenomics reads to known microbial sequences. However, microbial communities usually contain mixtures of hundreds to thousands of unknown bacteria. This restricts the accuracy and completeness of alignment-based approaches. The possibility of reference-free deconvolution of environmental sequencing data could benefit the field of metagenomics, contributing to the estimation of metagenome complexity, improving the metagenome assembly, and enabling the investigation of new bacterial species that are not visible using standard laboratory or alignment-based bioinformatics techniques.\n\nResultsHere, we apply an alignment-free method that leverages on k-mer frequencies to classify reads within a single long read metagenomic dataset. In addition to a series of simulated metagenomic datasets, we generated sequencing data from a bioreactor microbiome using the PacBio RSII single-molecule real-time sequencing platform. We show that distances obtained after the comparison of k-mer profiles can reveal relationships between reads within a single metagenome, leading to a clustering per species.\n\nConclusionsIn this study, we demonstrated the possibility to detect substructures within a single metagenome operating only with the information derived from the sequencing reads. The obtained results are highly important as they establish a principle that might potentially expand the toolkit for the detection and investigation of previously unknow microorganisms.

bioinformatics↗