The EMBL-EBI search and sequence analysis tools APIs in 2019.

The EMBL-EBI provides free access to popular bioinformatics sequence analysis applications as well as to a full-featured text search engine with powerful cross-referencing and data retrieval capabilities. Access to these services is provided via user-friendly web interfaces and via established RESTful and SOAP Web Services APIs (https://www.ebi.ac.uk/seqdb/confluence/display/JDSAT/EMBL-EBI+Web+Services+APIs+-+Data+Retrieval). Both systems have been developed with the same core principles that allow them to integrate an ever-increasing volume of biological data, making them an integral part of many popular data resources provided at the EMBL-EBI. Here, we describe the latest improvements made to the frameworks which enhance the interconnectivity between public EMBL-EBI resources and ultimately enhance biological data discoverability, accessibility, interoperability and reusability.

The EBI search engine: EBI search as a service-making biological data accessible for all.

We present an update of the EBI Search engine, an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types that include nucleotide and protein sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, as well as the life science literature. EBI Search provides a powerful RESTful API that enables its integration into third-party portals, thus providing 'Search as a Service' capabilities, which are the main topic of this article.

The EMBL-EBI bioinformatics web and programmatic tools framework.

Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community.

The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature.

Assembly information services in the European Nucleotide Archive.

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is a repository for the world public domain nucleotide sequence data output. ENA content covers a spectrum of data types including raw reads, assembly data and functional annotation. ENA has faced a dramatic growth in genome assembly submission rates, data volumes and complexity of datasets. This has prompted a broad reworking of assembly submission services, for which we now reach the end of a major programme of work and many enhancements have already been made available over the year to components of the submission service. In this article, we briefly review ENA content and growth over 2013, describe our rapidly developing services for genome assembly information and outline further major developments over the last year.

MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer.

Maturation of eukaryotic pre-mRNAs via splicing and polyadenylation is modulated across cell types and conditions by a variety of RNA-binding proteins (RBPs). Although there exist over 1,500 RBPs in human cells, their binding motifs and functions still remain to be elucidated, especially in the complex environment of tissues and in the context of diseases. To overcome the lack of methods for the systematic and automated detection of sequence motif-guided pre-mRNA processing regulation from RNA sequencing (RNA-Seq) data we have developed MAPP (Motif Activity on Pre-mRNA Processing). Applying MAPP to RBP knock-down experiments reveals that many RBPs regulate both splicing and polyadenylation of nascent transcripts by acting on similar sequence motifs. MAPP not only infers these sequence motifs, but also unravels the position-dependent impact of the RBPs on pre-mRNA processing. Interestingly, all investigated RBPs that act on both splicing and 3' end processing exhibit a consistently repressive or activating effect on both processes, providing a first glimpse on the underlying mechanism. Applying MAPP to normal and malignant brain tissue samples unveils that the motifs bound by the PTBP1 and RBFOX RBPs coordinately drive the oncogenic splicing program active in glioblastomas demonstrating that MAPP paves the way for characterizing pre-mRNA processing regulators under physiological and pathological conditions.

Biobtree: A tool to search, map and visualize bioinformatics identifiers and special keywords.

Due to their nature, bioinformatics datasets are often closely related to each other. For this reason, search, mapping and visualization of these relations are often performed manually or programmatically via identifiers or special keywords such as gene symbols. Although various tools exist for these situations, the growing volume of bioinformatics datasets, emerging new software tools and approaches motivates new solutions. To provide a new tool for these current cases, I present the Biobtree bioinformatics tool. Biobtree effectively fetches and indexes identifiers and special keywords with their related identifiers from supported datasets, optionally with user pre-defined datasets and provides a web interface, web services and direct B+ tree data structure based single uniform database output. Biobtree can handle billions of identifiers and runs via a single executable file with no installation and dependency required. It also aims to provide a relatively small codebase for easy maintenance, addition of new features and extension to larger datasets. Biobtree is available to download from GitHub.