From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF

Abstract

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/

The Stringent Stress Response Controls Proteases and Global Regulators under Optimal Growth Conditions in Pseudomonas aeruginosa

“…4B ). In the next step, the regulon of each regulator extracted from CollecTF ( 67 ) was further tested for statistical enrichment in the original list of differentially expressed genes, which revealed four significantly dysregulated regulons, AlgR ( P < 0.02), OxyR ( P < 0.02), LasR ( P < 0.01), and AmrZ ( P < 0.01); of these, only LasR was modestly 1.57-fold downregulated. The relevance of this analysis is indicated by the fact that global regulators like these control many downstream targets affected by the stringent response, as typified by LasR, a mediator of the 3-oxo-C12-acylhomoserinelactone-mediated quorum-sensing response ( 45 ).…”

“…The program was set to find up to five motifs, while all other settings were left at their defaults. These five de novo motifs found by MEME were then submitted to TomTom ( 90 ) to identify potential matches to characterized motifs and their corresponding regulators within the CollecTF database ( 67 ). Matches identified by TomTom were considered significant with a q value of ≤0.5.…”

“…The list of all PAO1 regulators and their controlled genes (regulon) was downloaded from CollecTF ( 67 ) or recent Chip-Seq manuscripts as indicated in the text. This list of regulons was then tested for enrichment in the list of 1,673 DE genes using Fisher’s exact test, implemented via a custom script in R. Multiple test correction was performed using the Benjamin-Hochberg (BH) method.…”

ECO, the Evidence & Conclusion Ontology: community standard for evidence information

“…Figure 3 describes term growth in ECO since 2014. This term growth has resulted from development efforts in collaboration with several of our user groups (including the Ontology of Microbial Phenotypes (OMP) (8), CollecTF (9), Disease Ontology (10) and GO) as well as from focused development efforts within the ECO team. Some of these efforts will be described in more detail below.…”

“…CollecTF is a resource that focuses on the capture of experimentally characterized bacterial transcription factors, their DNA targets and downstream regulated genes with an emphasis on the experimental provenance of curated records (9). This information is then integrated into central data repositories such as UniProt and the GO Annotation collection (9).…”