Biology subjects

de Ridder, D.

Publications and source records attributed to de Ridder, D..

8 recordsLinked to original sources

bioRxiv2018

poreTally: run and publish de novo Nanopore assembler benchmarks

Nanopore sequencing is a novel approach to nucleic acid analysis that generates long, error-prone reads. Since device components, base calling software and best practices for sample preparation are updated frequently and extensively, the nature of the produced data also changes frequently. As a result, peer-reviewed publications on de novo assembly pipeline benchmarking efforts are quickly rendered outdated by the next major improvement to the sequencing platforms. To provide the user community with a faster, more flexible alternative to peer-reviewed benchmark papers for de novo assembly tool performance we constructed poreTally, a comprehensive benchmarking tool. poreTally automatically assembles a given read set using several often-used assembly pipelines, analyzes the resulting assemblies for correctness and continuity, and finally generates a quality report. Results can immediately be shared with peers in a Github/Gitlab repository. Furthermore, we aim to give a more inclusive overview of assembly pipeline performance than any individual research group can, by offering users the possibility to submit their results to a collective benchmarking effort. poreTally is available on Github.

bioinformatics↗

bioRxiv2018

Family-based haplotype estimation and allele dosage correction for polyploids using short sequence reads

DNA sequence reads contain information about the genomic variants located on a single chromosome. By extracting and extending this information (using the overlaps of the reads), the haplotypes of an individual can be obtained. Adding parent-offspring relationships to the read information in a population can considerably improve the quality of the haplotypes obtained from short reads, as pedigree information can compensate for spurious overlaps (due to sequencing errors) and insufficient overlaps (due to shallow coverage). This improvement is especially beneficial for polyploid organisms, which have more than two copies of each chromosome and are therefore more difficult to be haplotyped compared to diploids. We develop a novel method, PopPoly, to estimate polyploid haplotypes in an F1-population from short sequence data by considering the transmission of the haplotypes from the parents to the offspring. In addition, PopPoly employs this information to improve genotype dosage estimation and to call missing genotypes in the population. Through realistic simulations, we compare PopPoly to other haplotyping methods and show its better performance in terms of phasing accuracy and the accuracy of phased genotypes. We apply PopPoly to estimate the parental and offspring haplotypes for a tetraploid potato cross with 10 offspring, using Illumina HiSeq sequence data of 9 genomic regions involved in plant maturity and tuberisation.

bioinformatics↗

bioRxiv2018

Improving intermolecular contact prediction through protein-protein interaction prediction using coevolutionary analysis with expectation-maximization

Predicting residue-residue contacts between interacting proteins is an important problem in bioinformatics. The growing wealth of sequence data can be used to infer these contacts through correlated mutation analysis on multiple sequence alignments of interacting homologs of the proteins of interest. This requires correct identification of pairs of interacting proteins for many species, in order to avoid introducing noise (i.e. non-interacting sequences) in the analysis that will decrease predictive performance. We have designed Ouroboros, a novel algorithm to reduce such noise in intermolecular contact prediction. Our method iterates between weighting proteins according to how likely they are to interact based on the correlated mutations signal, and predicting correlated mutations based on the weighted sequence alignment. We show that this approach accurately discriminates between protein interaction versus noninteraction and simultaneously improves the prediction of intermolecular contact residues compared to a naive application of correlated mutation analysis. Furthermore, the method relaxes the assumption of one-to-one interaction of previous approaches, allowing for the study of many-to-many interactions. Source code and test data are available at www.bif.wur.nl/

bioinformatics↗

bioRxiv2017

Correcting palindromes in long reads after whole-genome amplification

Next-generation sequencing requires sufficient DNA to be available. If limited, whole-genome amplification is applied to generate additional amounts of DNA. Such amplification often results in many chimeric DNA fragments, in particular artificial palindromic sequences, which limit the usefulness of long reads from technologies such as PacBio and Oxford Nanopore. Here, we present Pacasus, a tool for correcting such errors in long reads. We demonstrate on two real-world datasets that it markedly improves subsequent read mapping and de novo assembly, yielding results similar to these that would be obtained with non-amplified DNA. With Pacasus long-read technologies become readily available for sequencing targets with very small amounts of DNA, such as single cells or even single chromosomes.

genomics↗

bioRxiv2017

Genome-wide characterization of Phytophthora infestansmetabolism: a systems biology approach

Genome-scale metabolic models (GEMs) provide a functional view of the complex network of biochemical reactions in the living cell. Initially mainly applied to reconstruct the metabolism of model organisms, the availability of increasingly sophisticated reconstruction methods and more extensive biochemical databases now make it possible to reconstruct GEMs for less characterized organisms as well, and have the potential to unravel the metabolism in pathogen-host systems. Here we present a GEM for the oomycete plant pathogen Phytophthora infestans as a first step towards an integrative model with its host. We predict the biochemical reactions in different cellular compartments and investigate the gene-protein-reaction associations in this model to get an impression of the biochemical capabilities of P. infestans. Furthermore, we generate life stage-specific models to place the transcriptomic changes of genes encoding metabolic enzymes into a functional context. In sporangia and zoospores there is an overall downregulation, most strikingly reflected in the fatty acid biosynthesis pathway. To investigate the robustness of the GEM, we simulate gene deletions to predict which enzymes are essential for in vitro growth. While there is room for improvement, this first model is an essential step towards an understanding of P. infestans and its interactions with plants as a system, which will help to formulate new hypotheses on infection mechanisms and disease prevention.

systems biology↗

bioRxiv2017

TriPoly: a haplotype estimation approach for polyploids using sequencing data of related individuals

Knowledge of \"haplotypes\", i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci (QTL).\n\nWe propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of short- read sequencing data for potato (Solanum tuberosum) and banana (Musa acuminata) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to the existing methods that work on single individuals.

bioinformatics↗

bioRxiv2017

A Sequencer Coming Of Age: De Novo Genome Assembly Using MinION Reads

Nanopore technology provides a novel approach to DNA sequencing that yields long, label-free reads of constant quality. The first commercial implementation of this approach, the MinION, has shown promise in various sequencing applications. The presented literature review gives an up-to-date overview of the MinIONs utility as a de novo sequencing device. It is argued that the MinION may allow for portable and affordable de novo sequencing of even complex genomes in the near future, despite the currently error-prone nature of its reads. Through continuous updates to the MinION hardware and the development of new assembly pipelines, both sequencing accuracy and assembly quality have already risen rapidly. However, this fast pace of development has also lead to a lack of oversight in the expanding landscape of analysis tools, as performance evaluations are outdated quickly. Now that the MinION is approaching a state of maturity, a thorough comparative benchmarking effort of de novo assembly pipelines may be at place.

genetics↗

bioRxiv2016

Exploiting Next Generation Sequencing to solve the Haplotyping puzzle in Polyploids: a Simulation study

Haplotypes are the units of inheritance in an organism, and many genetic analyses depend on their precise determination. Methods for haplotyping single individuals use the phasing information available in Next Generation sequencing reads, by matching overlapping sNPs while penalizing post hoc nucleotide corrections made. Haplotyping diploids is relatively easy, but the complexity of the problem increases drastically for polyploid genomes, which are found in both model organisms and in economically relevant plant and animal species. While a number of tools are available for haplotyping polyploids, the effects of the genomic makeup and the sequencing strategy followed on the accuracy of these methods have hitherto not been thoroughly evaluated.\n\nWe developed the simulation pipeline haplosim to evaluate the performance of haplotype estimation algorithms for polyploids: HapCompass, HapTree and SDhaP, in settings varying in sequencing approach, ploidy levels and genomic diversity, using tetraploid potato as the model. Our results show that sequencing depth is the major determinant of haplotype estimation quality, that 1kb PacBio CCS reads and Illumina reads with large insert-sizes are competitive, and that all methods fail to produce good haplotypes when ploidy levels increase. Comparing the three methods, HapTree produces the most accurate estimates, but also consumes the most resources. There is clearly room for improvement in polyploid haplotyping algorithms.

bioinformatics↗