Search

Motivation Antibodies play essential roles in the immune system of vertebrates and are powerful tools in research and diagnostics. While hypervariable regions of antibodies, which are responsible for binding, can be readily identified from their amino acid sequence, it remains challenging to accurately pinpoint which amino acids will be in contact with the antigen (the paratope). Results In this work, we present a sequence-based probabilistic machine learning algorithm for paratope prediction, named Parapred. Parapred uses a deep-learning architecture to leverage features from both local residue neighbourhoods and across the entire sequence. The method significantly improves on the current state-of-the-art methodology, and only requires a stretch of amino acid sequence corresponding to a hypervariable region as an input, without any information about the antigen. We further show that our predictions can be used to improve both speed and accuracy of a rigid docking algorithm. Availability and implementation The Parapred method is freely available as a webserver at http://www-mvsoftware.ch.cam.ac.uk/and for download at https://github.com/eliberis/parapred. Supplementary information Supplementary information is available at Bioinformatics online.

Motivation: Recent advancements in molecular methods have made it possible to capture physical contacts between multiple chromatin fragments. The resulting association matrices provide a noisy estimate for average spatial proximity that can be used to gain insights into the genome organization inside the nucleus. However, extracting topological information from these data is challenging and their integration across resolutions is still poorly addressed. Recent findings suggest that a hierarchical approach could be advantageous for addressing these challenges. Results: We present an algorithmic framework, which is based on hierarchical block matrices (HBMs), for topological analysis and integration of chromosome conformation capture (3C) data. We first describe chromoHBM, an algorithm that compresses high-throughput 3C (HiT-3C) data into topological features that are efficiently summarized with an HBM representation. We suggest that instead of directly combining HiT-3C datasets across resolutions, which is a difficult task, we can integrate their HBM representations, and describe chromoHBM-3C, an algorithm which merges HBMs. Since three-dimensional (3D) reconstruction can also benefit from topological information, we further present chromoHBM-3D, an algorithm which exploits the HBM representation in order to gradually introduce topological constraints to the reconstruction process. We evaluate our approach in light of previous image microscopy findings and epigenetic data, and show that it can relate multiple spatial scales and provide a more complete view of the 3D genome architecture. Availability and implementation: The presented algorithms are available from: https://github.com/yolish/hbm. Contact: ys388@cam.ac.uk or pl219@cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: With the development of experimental methods and technology, we are able to reliably gain access to data in larger quantities, dimensions and types. This has great potential for the improvement of machine learning (as the learning algorithms have access to a larger space of information). However, conventional machine learning approaches used thus far on single-dimensional data inputs are unlikely to be expressive enough to accurately model the problem in higher dimensions; in fact, it should generally be most suitable to represent our underlying models as some form of complex networksng;nsio with nontrivial topological features. As the first step in establishing such a trend, we present muxstep, an open-source library utilising multiplex networks for the purposes of binary classification on multiple data types. The library is designed to be used out-of-the-box for developing models based on the multiplex network framework, as well as easily modifiable to suit problem modelling needs that may differ significantly from the default approach described. Availability and Implementation: The full source code is available on GitHub: https://github.com/PetarV-/muxstep Contact: petar.velickovic@cl.cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

Summary: CytoCom is an interactive plugin for Cytoscape that can be used to search, explore, analyse and visualize human disease comorbidity network. It represents disease–disease associations in terms of bipartite graphs and provides International Classification of Diseases, Ninth Revision (ICD9)-centric and disease name centric views of disease information. It allows users to find associations between diseases based on the two measures: Relative Risk (RR) and ϕ-correlation values. In the disease network, the size of each node is based on the prevalence of that disease. CytoCom is capable of clustering disease network based on the ICD9 disease category. It provides user-friendly access that facilitates exploration of human diseases, and finds additional associated diseases by double-clicking a node in the existing network. Additional comorbid diseases are then connected to the existing network. It is able to assist users for interpretation and exploration of the human diseases by a variety of built-in functions. Moreover, CytoCom permits multi-colouring of disease nodes according to standard disease classification for expedient visualization. Availability and implementation: CytoCom is compatible with CytoScape 3.1.0 or later version. Please visit http://www.cl.cam.ac.uk/∼mam211/ for user tutorial and download. Contact: Mohammad.Moni@cl.cam.ac.uk

Motivation: At a recent meeting†, the wavelet transform was depicted as a small child kicking back at its father, the Fourier transform. Wavelets are more efficient and faster than Fourier methods in capturing the essence of data. Nowadays there is a growing interest in using wavelets in the analysis of biological sequences and molecular biology-related signals. Results: This review is intended to summarize the potential of state of the art wavelets, and in particular wavelet statistical methodology, in different areas of molecular biology: genome sequence, protein structure and microarray data analysis. I conclude by discussing the use of wavelets in modeling biological structures. Contact: plio@hgmp.mrc.ac.uk † XIX SMC 2001 ‘Wavelets in Statistics’, Vico Equense, Naples, I, 2–7 April 2001.

Motivation: A non-parametric method, based on a wavelet data-dependent threshold technique for change-point analysis, is applied to predict location and topology of helices in transmembrane proteins. A new propensity scale generated from a transmembrane helix database is proposed. Results: We show that wavelet change-point performs well for smoothing hydropathy and transmembrane profiles generated using different scales. We investigate which wavelet bases and threshold functions are overall most appropriate to detect transmembrane segments. Prediction accuracy is based on the analysis of two data sets used as standard benchmarks for transmembrane prediction algorithms. The analysis of a test set of 83 proteins results in accuracy per segment equal to 98.2%; the analysis of a 48 proteins blind-test set, i.e. containing proteins not used to generate the propensity scales, results in accuracy per segment equal to 97.4%. We believe that this method can also be applied to the detection of boundaries of other patterns such as G + Cisochores and dot-plots. Availability: The transmembrane database, TMALN and source code are available upon request from the authors. Contact: plio@hgmp.mrc.ac.uk

Summary: We describe an algorithm and software tool for comparing alternative phylogenetic trees. The main application of the software is to compare phylogenies obtained using different phylogenetic methods for some fixed set of species or obtained using different gene sequences from those species. The algorithm pairs up each branch in one phylogeny with a matching branch in the second phylogeny and finds the optimum 1-to-1 map between branches in the two trees in terms of a topological score. The software enables the user to explore the corresponding mapping between the phylogenies interactively, and clearly highlights those parts of the trees that differ, both in terms of topology and branch length. Availability: The software is implemented as a Java applet at . It is also available on request from the authors. Contact: thomas.nye@mrc-bsu.cam.ac.uk

Summary: With the introduction of the Hi-C method new and fundamental properties of the nuclear architecture are emerging. The ability to interpret data generated by this method, which aims to capture the physical proximity between and within chromosomes, is crucial for uncovering the three dimensional structure of the nucleus. Providing researchers with tools for interactive visualization of Hi-C data can help in gaining new and important insights. Specifically, visual comparison can pinpoint changes in spatial organization between Hi-C datasets, originating from different cell lines or different species, or normalized by different methods. Here, we present CytoHiC, a Cytsocape plugin, which allow users to view and compare spatial maps of genomic landmarks, based on normalized Hi-C datasets. CytoHiC was developed to support intuitive visual comparison of Hi-C data and integration of additional genomic annotations. Availability: The CytoHiC plugin, source code, user manual, example files and documentation are available at: http://apps.cytoscape.org/apps/cytohicplugin Contact: yolisha@gmail.com or ys388@cam.ac.uk