Functional analysis of large gene lists, derived in most cases from emerging high-throughput genomic, proteomic and bioinformatics scanning approaches, is still a challenging and daunting task. The gene-annotation enrichment analysis is a promising high-throughput strategy that increases the likelihood for investigators to identify biological processes most pertinent to their study. Approximately 68 bioinformatics enrichment tools that are currently available in the community are collected in this survey. Tools are uniquely categorized into three major classes, according to their underlying enrichment algorithms. The comprehensive collections, unique tool classifications and associated questions/issues will provide a more comprehensive and up-to-date view regarding the advantages, pitfalls and recent trends in a simpler tool-class level rather than by a tool-by-tool approach. Thus, the survey will help tool designers/developers and experienced end users understand the underlying algorithms and pertinent details of particular tool categories/tools, enabling them to make the best choices for their particular research interests.

/pdf/bioinformatics-enrichment-tools-paths-toward-the-2yo1xl3r2j.pdf

Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

/pdf/diagnostic-criteria-for-multiple-sclerosis-2010-revisions-to-24iph50480.pdf

Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

https://www.bioinf.uni-leipzig.de/Leere/WS1516/SeqAnalGen/T-Coffee.pdf

T-Coffee: A novel method for fast and accurate multiple sequence alignment.

A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era

/pdf/metascape-provides-a-biologist-oriented-resource-for-the-1ovoy8ih4d.pdf

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets.

Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

/pdf/new-contact-measures-for-the-protein-docking-problem-1sm8s0nxxm.pdf

New contact measures for the protein docking problem

Nous nous interessons a la question de l'ajout de restrictions de domaine aux problemes de recherche decomposables. D'abord, nous donnons une technique generale qui rend partiellement persistante une structure de donnees arbitraire. Ensuite, nous donnons une technique generale qui transforme une structure de donnees partiellement persistante resolvant un probleme de recherche decomposable, en une structure pour le meme probleme mais soumis a des contraintes supplementaires. L'application de cette technique generale a des problemes specifiques de recherche, fournit des structures de donnees efficaces, particulierement dans le cas ou plus d'une seule restriction de domaine est ajoutee, l'une d'entre elles ayant au moins une constante

Using persistent data structures for adding range restrictions to searching problems

Adjusting intracellular calcium signaling is an important feature in the regulation of immune cell function and survival. Here we show that miR-34a-5p, a small non-coding RNA that is deregulated in many common diseases, is a regulator of store-operated Ca2+ entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca2+ influx through Ca2+ release-activated Ca2+ channels. Based on an in silico target prediction we identified multiple miR-34a-5p target genes within both pathways that are implicated in the balance between T-cell activation and apoptosis including ITPR2, CAMLG, STIM1, ORAI3, RCAN1, PPP3R1, and NFATC4. Functional analysis revealed a decrease in Ca2+ activated calcineurin pathway activity measured by a reduced IL-2 secretion due to miR-34a-5p overexpression. Impacting SOCE and/or downstream calcineurin/NFAT signaling by miR-34a-5p offers a possible future approach to manipulate immune cells for clinical interventions.

/pdf/modulation-of-intracellular-calcium-signaling-by-microrna-12xu9r4vro.pdf

Modulation of intracellular calcium signaling by microRNA-34a-5p.

Molecular geometric properties, such as volume, exposed surface area, and occurrence of internal cavities, are important inputs to many applications in molecular modeling. In this work we describe a very general and highly efficient approach for the accurate computation of such properties, which is applicable to arbitrary molecular surface models. The technique relies on a high performance ray casting framework that can be easily adapted to the computation of further quantities of interest at interactive speed, even for huge models.

/pdf/measuring-properties-of-molecular-surfaces-using-ray-casting-5685fawi4p.pdf

Measuring properties of molecular surfaces using ray casting

Motivation: Sequence-based phylogenetic approaches heavily rely on initial data sets to be composed of orthologous sequences only. Paralogs are treated as a dangerous nuisance that has to be detected and removed. Recent advances in mathematical phylogenetics, however, have indicated that gene duplications can also convey meaningful phylogenetic information provided orthologs and paralogs can be distinguished with a degree of certainty. Results: We demonstrate that plausible phylogenetic trees can be inferred from paralogy information only. To this end, tree-free estimates of orthology, the complement of paralogy, are first corrected to conform cographs and then translated into equivalent event-labeled gene phylogenies. A certain subset of the triples displayed by these trees translates into constraints on the species trees. While the resolution is very poor for individual gene families, we observe that genome-wide data sets are sufficient to generate fully resolved phylogenetic trees of several groups of eubacteria. The novel method introduced here relies on solving three intertwined NP-hard optimization problems: the cograph editing problem, the maximum consistent triple set problem, and the least resolved tree problem. Implemented as Integer Linear Program, paralogy-based phylogenies can be computed exactly for up to some twenty species and their complete protein complements. Availability: The ILP formulation is implemented in the Software ParaPhylo using IBM ILOG CPLEX TM Optimizer 12.6 and is freely available from http://pacosy.informatik.uni-leipzig.de/ paraphylo.

/pdf/phylogenetics-from-paralogs-2vikfp1bm4.pdf

Hans-Peter Lenhof

Papers

New contact measures for the protein docking problem

Using persistent data structures for adding range restrictions to searching problems

Modulation of intracellular calcium signaling by microRNA-34a-5p.

Measuring properties of molecular surfaces using ray casting

Phylogenetics from paralogs