Life sciences are yielding huge data sets that underpin scientific discoveries fundamental to improvement in human health, agriculture and the environment. In support of these discoveries, a plethora of databases and tools are deployed, in technically complex and diverse implementations, across a spectrum of scientific disciplines. The corpus of documentation of these resources is fragmented across the Web, with much redundancy, and has lacked a common standard of information. The outcome is that scientists must often struggle to find, understand, compare and use the best resources for the task at hand.Here we present a community-driven curation effort, supported by ELIXIR—the European infrastructure for biological information—that aspires to a comprehensive and consistent registry of information about bioinformatics resources. The sustainable upkeep of this Tools and Data Services Registry is assured by a curation effort driven by and tailored to local needs, and shared amongst a network of engaged partners.As of November 2015, the registry includes 1785 resources, with depositions from 126 individual registrations including 52 institutional providers and 74 individuals. With community support, the registry can become a standard for dissemination of information about bioinformatics resources: we welcome everyone to join us in this common endeavour. The registry is freely available at https://bio.tools.
Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via vaccination. Classically, these models are defined in terms of a probabilistic V(D)J recombination model which is sometimes combined with a selection model. In this paper we take a different approach, fitting variational autoencoder (VAE) models parameterized by deep neural networks to T cell receptor (TCR) repertoires. We show that simple VAE models can perform accurate cohort frequency estimation, learn the rules of VDJ recombination, and generalize well to unseen sequences. Further, we demonstrate that VAE-like models can distinguish between real sequences and sequences generated according to a recombination-selection model, and that many characteristics of VAE-generated sequences are similar to those of real sequences.
B cell receptor sequences evolve during affinity maturation according to a Darwinian process of mutation and selection. Phylogenetic tools are used extensively to reconstruct ancestral sequences and phylogenetic trees from affinity-matured sequences. In addition to using general-purpose phylogenetic methods, researchers have developed new tools to accommodate the special features of B cell sequence evolution. However, the performance of classical phylogenetic techniques in the presence of B cell-specific features is not well understood, nor how much the newer generation of B cell specific tools represent an improvement over classical methods. In this paper we benchmark the performance of classical phylogenetic and new B cell-specific tools when applied to B cell receptor sequences simulated from a forward-time model of B cell receptor affinity maturation toward a mature receptor. We show that the currently used tools vary substantially in terms of tree structure and ancestral sequence inference accuracy. Furthermore, we show that there are still large performance gains to be achieved by modeling the special mutation process of B cell receptors. These conclusions are further strengthened with real data using the rules of isotype switching to count possible violations within each inferred phylogeny.
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