Biology subjects

Laukens, K.

Publications and source records attributed to Laukens, K..

6 recordsLinked to original sources

bioRxiv2018

TCRex: a webtool for the prediction of T-cell receptor sequence epitope specificity

High-throughput T cell receptor (TCR) sequencing allows the characterization of an individuals TCR repertoire and directly query their immune state. However, it remains a non-trivial task to couple these sequenced TCRs to their antigenic targets. In this paper, we present a novel strategy to annotate full TCR sequence repertoires. The strategy is based on a machine learning algorithm to learn the TCR patterns common to the recognition of a specific epitope. These results are then combined with a statistical analysis to evaluate the occurrence of specific epitope-reactive TCR sequences per epitope in repertoire data. In this manner, we can directly study the capacity of full TCR repertoires to target specific epitopes of the relevant vaccines or pathogens. We demonstrate the usability of this approach on three independent datasets related to vaccine monitoring and infectious disease diagnostics by independently identifying the epitopes that are targeted by the TCR repertoire. The developed method is freely available as a web tool for academic use at tcrex.biodatamining.be.

bioinformatics↗

bioRxiv2018

Fast open modification spectral library searching through approximate nearest neighbor indexing

Open modification searching (OMS) is a powerful search strategy that identifies peptides carrying any type of modification by allowing a modified spectrum to match against its unmodified variant by using a very wide precursor mass window. A drawback of this strategy, however, is that it leads to a large increase in search time. Although performing an open search can be done using existing spectral library search engines by simply setting a wide precursor mass window, none of these tools have been optimized for OMS, leading to excessive runtimes and suboptimal identification results. Here we present the ANN-SoLo tool for fast and accurate open spectral library searching. ANN-SoLo uses approximate nearest neighbor indexing to speed up OMS by selecting only a limited number of the most relevant library spectra to compare to an unknown query spectrum. This approach is combined with a cascade search strategy to maximize the number of identified unmodified and modified spectra while strictly controlling the false discovery rate, as well as a shifted dot product score to sensitively match modified spectra to their unmodified counterparts. ANN-SoLo achieves state-of-the-art performance in terms of speed and the number of identifications. On a previously published human cell line data set, ANN-SoLo confidently identifies more spectra than SpectraST or MSFragger and achieves a speedup of an order of magnitude compared to SpectraST.\n\nANN-SoLo is implemented in Python and C++. It is freely available under the Apache 2.0 license at https://github.com/bittremieux/ANN-SoLo.

bioinformatics↗

bioRxiv2018

The workings and failings of clustering T-cell receptor beta-chain sequences without a known epitope preference

The T-cell receptor is responsible for recognizing potentially harmful epitopes presented on cell surfaces. The binding rules that govern this recognition between receptor and epitope is currently an unsolved problem, yet one of great interest. Several methods have been proposed recently to perform supervised classification of T-cell receptor sequences, but this requires known examples of T-cell sequences for a given epitope. Here we study the viability of various methods to perform unsupervised clustering of distinct T-cell receptor sequences and how these clusters relate to their target epitope. The goal is to provide an overview of the performance of various distance metrics on two large independent T-cell receptor sequence data sets. Our results confirm the presence of structural distinct T-cell groups that target identical epitopes. In addition, we put forward several recommendations to perform T-cell receptor sequence clustering.

bioinformatics↗

bioRxiv2017

speaq 2.0: A Wavelet-Based Workflow For High-Throughput 1D NMR Spectra Processing And Quantification

Nuclear Magnetic Resonance (NMR) spectroscopy is, together with liquid chromatography-mass spectrometry (LC-MS), the most established platform to perform metabolomics. In contrast to LC-MS however, NMR data is predominantly being processed with commercial software. This has the effect that its data processing remains tedious and dependent on user interventions. As a follow-up to speaq, a previously released workflow for NMR spectral alignment and quantitation, we present speaq 2.0. This completely revised framework to automatically analyze 1D NMR spectra uses wavelets to efficiently summarize the raw spectra with minimal information loss or user interaction. The tool offers a fast and easy workflow that starts with the common approach of peak-picking, followed by grouping. This yields a matrix consisting of features, samples and peak values that can be conveniently processed either by using included multivariate statistical functions or by using many other recently developed methods for NMR data analysis. speaq 2.0 facilitates robust and high-throughput metabolomics based on 1D NMR but is also compatible with other NMR frameworks or complementary LC-MS workflows. The methods are benchmarked using two publicly available datasets. speaq 2.0 is distributed through the existing speaq R package to provide a complete solution for NMR data processing. The package and the code for the presented case studies are freely available on CRAN (https://cran.r-project.org/package=speaq) and GitHub (https://github.com/beirnaert/speaq).\n\nAuthor summaryWe present speaq 2.0: a user friendly workflow for processing NMR spectra quickly and easily. By limiting the need for user interaction and allowing the construction of workflows by combining R functions, metabolomics data analysis becomes fully reproducible and shareable. Such advances are critical for the future of the metabolomics field as it needs to move towards a fully open-science approach. This is no trivial goal as many researchers are still using black-box commercial software that often requires manually doing several steps, thus hampering reproducibility. To encourage the shift towards open source, we deliberately made our method usable for anyone with the most basic of R experience, something that is easily acquired. speaq 2.0 allows a stand-alone analysis from spectra to statistical analysis. In addition, the package can be combined with existing tools to improve performance, as it provides a superior peak picking method compared to the standard binning approach.

bioinformatics↗

bioRxiv2017

Automated Recommendation Of Metabolite Substructures From Mass Spectra Using Frequent Pattern Mining

Despite the increasing importance of non-targeted metabolomics to answer various life science questions, extracting biochemically relevant information from metabolomics spectral data is still an incompletely solved problem. Most computational tools to identify tandem mass spectra focus on a limited set of molecules of interest. However, such tools are typically constrained by the availability of reference spectra or molecular databases, limiting their applicability to identify unknown metabolites. In contrast, recent advances in the field illustrate the possibility to expose the underlying biochemistry without relying on metabolite identification, in particular via substructure prediction. We describe an automated method for substructure recommendation motivated by association rule mining. Our framework captures potential relationships between spectral features and substructures learned from public spectral libraries. These associations are used to recommend substructures for any unknown mass spectrum. Our method does not require any predefined metabolite candidates, and therefore it can be used for the partial identification of unknown unknowns. The method is called MESSAR (MEtabolite SubStructure Auto-Recommender) and is implemented in a free online web service available at messar.biodatamining.be.\n\nAuthor SummaryMass spectrometry is one of most used techniques to detect and identify metabolites. However, learning metabolite structures directly from mass spectrometry data has always been a challenging task. Thousands of mass spectra from various biological systems still remain unanalyzed simply because no current bioinformatic tools are able to generate structural hypotheses. By manually studying mass spectra of standard compounds, chemists discovered that metabolites that share common substructures can also share spectral features. As data scientists, we believe that such relationships can be unraveled from massive structure and spectra data by machine learning. In this study, we adapted \"association rule mining\", traditionally used in market basket analysis, to structural and spectral data, allowing us to investigate all spectral features - metabolite substructures relationships. We further collected all statistically sound relationships into a database and used them to assign substructral hypotheses to unexplored spectra. We named our approach MESSAR, MEtabolite SubStructure Auto-Recommender, available to the metabolomics and mass spectrometry community as a free and open web service.

bioinformatics↗

bioRxiv2017

On the feasibility of mining CD8+ T-cell receptor patterns underlying immunogenic peptide recognition.

AbstractCurrent T-cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T-cell receptor is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T-cell and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of T-cell receptors that each bind to a known peptide and (2) retrieving T-cell receptors that bind to a given peptide from a large pool of T-cell receptors. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particularly importance as they show that prediction of T-cell epitope and T-cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T-cell epitopes but also paves the way for more general and high performing models.

immunology↗