PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3' end sequencing.

Generated by 3' end cleavage and polyadenylation at alternative polyadenylation (poly(A)) sites, alternative terminal exons account for much of the variation between human transcript isoforms. More than a dozen protocols have been developed so far for capturing and sequencing RNA 3' ends from a variety of cell types and species. In previous studies, we have used these data to uncover novel regulatory signals and cell type-specific isoforms. Here we present an update of the PolyASite (https://polyasite.unibas.ch) resource of poly(A) sites, constructed from publicly available human, mouse and worm 3' end sequencing datasets by enforcing uniform quality measures, including the flagging of putative internal priming sites. Through integrated processing of all data, we identified and clustered sites that are closely spaced and share polyadenylation signals, as these are likely the result of stochastic variations in processing. For each cluster, we identified the representative - most frequently processed - site and estimated the relative use in the transcriptome across all samples. We have established a modern web portal for efficient finding, exploration and export of data. Database generation is fully automated, greatly facilitating incorporation of new datasets and the updating of underlying genome resources.

The ISMARA client.

ISMARA ( ismara.unibas.ch) automatically infers the key regulators and regulatory interactions from high-throughput gene expression or chromatin state data. However, given the large sizes of current next generation sequencing (NGS) datasets, data uploading times are a major bottleneck. Additionally, for proprietary data, users may be uncomfortable with uploading entire raw datasets to an external server. Both these problems could be alleviated by providing a means by which users could pre-process their raw data locally, transferring only a small summary file to the ISMARA server. We developed a stand-alone client application that pre-processes large input files (RNA-seq or ChIP-seq data) on the user's computer for performing ISMARA analysis in a completely automated manner, including uploading of small processed summary files to the ISMARA server. This reduces file sizes by up to a factor of 1000, and upload times from many hours to mere seconds. The client application is available from ismara.unibas.ch/ISMARA/client.

Coev-web: a web platform designed to simulate and evaluate coevolving positions along a phylogenetic tree.

BACKGROUND: Available methods to simulate nucleotide or amino acid data typically use Markov models to simulate each position independently. These approaches are not appropriate to assess the performance of combinatorial and probabilistic methods that look for coevolving positions in nucleotide or amino acid sequences. RESULTS: We have developed a web-based platform that gives a user-friendly access to two phylogenetic-based methods implementing the Coev model: the evaluation of coevolving scores and the simulation of coevolving positions. We have also extended the capabilities of the Coev model to allow for the generalization of the alphabet used in the Markov model, which can now analyse both nucleotide and amino acid data sets. The simulation of coevolving positions is novel and builds upon the developments of the Coev model. It allows user to simulate pairs of dependent nucleotide or amino acid positions. CONCLUSIONS: The main focus of our paper is the new simulation method we present for coevolving positions. The implementation of this method is embedded within the web platform Coev-web that is freely accessible at http://coev.vital-it.ch/, and was tested in most modern web browsers.

ExPASy: SIB bioinformatics resource portal.

ExPASy (http://www.expasy.org) has worldwide reputation as one of the main bioinformatics resources for proteomics. It has now evolved, becoming an extensible and integrative portal accessing many scientific resources, databases and software tools in different areas of life sciences. Scientists can henceforth access seamlessly a wide range of resources in many different domains, such as proteomics, genomics, phylogeny/evolution, systems biology, population genetics, transcriptomics, etc. The individual resources (databases, web-based and downloadable software tools) are hosted in a 'decentralized' way by different groups of the SIB Swiss Institute of Bioinformatics and partner institutions. Specifically, a single web portal provides a common entry point to a wide range of resources developed and operated by different SIB groups and external institutions. The portal features a search function across 'selected' resources. Additionally, the availability and usage of resources are monitored. The portal is aimed for both expert users and people who are not familiar with a specific domain in life sciences. The new web interface provides, in particular, visual guidance for newcomers to ExPASy.