DMLS: an automated pipeline to extract the Drosophila modular transcription regulators and targets from massive literature articles.

Transcription regulation in multicellular species is mediated by modular transcription factor (TF) binding site combinations termed cis-regulatory modules (CRMs). Such CRM-mediated transcription regulation determines the gene expression patterns during development. Biologists frequently investigate CRM transcription regulation on gene expressions. However, the knowledge of the target genes and regulatory TFs participating in the CRMs under study is mostly fragmentary throughout the literature. Researchers need to afford tremendous human resources to fully surf through the articles deposited in biomedical literature databases in order to obtain the information. Although several novel text-mining systems are now available for literature triaging, these tools do not specifically focus on CRM-related literature prescreening, failing to correctly extract the information of the CRM target genes and regulatory TFs from the literature. For this reason, we constructed a supportive auto-literature prescreener called Drosophila Modular transcription-regulation Literature Screener (DMLS) that achieves the following: (i) prescreens articles describing experiments on modular transcription regulation, (ii) identifies the described target genes and TFs of the CRMs under study for each modular transcription-regulation-describing article and (iii) features an automated and extendable pipeline to perform the task. We demonstrated that the final performance of DMLS in extracting the described target gene and regulatory TF lists of CRMs under study for given articles achieved test macro area under the ROC curve (auROC) = 89.7% and area under the precision-recall curve (auPRC) = 77.6%, outperforming the intuitive gene name-occurrence-counting method by at least 19.9% in auROC and 30.5% in auPRC. The web service and the command line versions of DMLS are available at https://cobis.bme.ncku.edu.tw/DMLS/  and  https://github.com/cobisLab/DMLS/, respectively. Database Tool URL: https://cobis.bme.ncku.edu.tw/DMLS/.

YTLR: Extracting yeast transcription factor-gene associations from the literature using automated literature readers.

Cells adapt to environmental stresses mainly via transcription reprogramming. Correct transcription control is mediated by the interactions between transcription factors (TF) and their target genes. These TF-gene associations can be probed by chromatin immunoprecipitation techniques and knockout experiments, revealing TF binding (TFB) and regulatory (TFR) evidence, respectively. Nevertheless, most evidence is still fragmentary in the literature and requires tremendous human resources to curate. We developed the first pipeline called YTLR (Yeast Transcription-regulation Literature Reader) to automate TF-gene relation extraction from the literature. YTLR first identifies articles with TFB and TFR information. Then TF-gene binding pairs are extracted from the TFB articles, and TF-gene regulatory associations are recognized from the TFR papers. On gathered test sets, YTLR achieves an AUC value of 98.8% in identifying articles with TFB evidence and AUC = 83.4% in extracting the detailed TF-gene binding pairs. And similarly, YTLR also obtains an AUC value of 98.2% in identifying TFR articles and AUC = 80.4% in extracting the detailed TF-gene regulatory associations. Furthermore, YTLR outperforms previous methods in both tasks. To facilitate researchers in extracting TF-gene transcriptional relations from large-scale queried articles, an automated and easy-to-use software tool based on the YTLR pipeline is constructed. In summary, YTLR aims to provide easier literature pre-screening for curators and help researchers gather yeast TF-gene transcriptional relation conclusions from articles in a high-throughput fashion. The YTLR pipeline software tool can be downloaded at https://github.com/cobisLab/YTLR/.

Human IRES Atlas: an integrative platform for studying IRES-driven translational regulation in humans.

It is now known that cap-independent translation initiation facilitated by internal ribosome entry sites (IRESs) is vital in selective cellular protein synthesis under stress and different physiological conditions. However, three problems make it hard to understand transcriptome-wide cellular IRES-mediated translation initiation mechanisms: (i) complex interplay between IRESs and other translation initiation-related information, (ii) reliability issue of in silico cellular IRES investigation and (iii) labor-intensive in vivo IRES identification. In this research, we constructed the Human IRES Atlas database for a comprehensive understanding of cellular IRESs in humans. First, currently available and suitable IRES prediction tools (IRESfinder, PatSearch and IRESpy) were used to obtain transcriptome-wide human IRESs. Then, we collected eight genres of translation initiation-related features to help study the potential molecular mechanisms of each of the putative IRESs. Three functional tests (conservation, structural RNA-protein scores and conditional translation efficiency) were devised to evaluate the functionality of the identified putative IRESs. Moreover, an easy-to-use interface and an IRES-translation initiation interaction map for each gene transcript were implemented to help understand the interactions between IRESs and translation initiation-related features. Researchers can easily search/browse an IRES of interest using the web interface and deduce testable mechanism hypotheses of human IRES-driven translation initiation based on the integrated results. In summary, Human IRES Atlas integrates putative IRES elements and translation initiation-related experiments for better usage of these data and deduction of mechanism hypotheses. Database URL: http://cobishss0.im.nuk.edu.tw/Human_IRES_Atlas/.