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Genomics has set the basis for a variety of methodologies that produce high-throughput datasets identifying the different players that define gene regulation, particularly regulation of transcription initiation and operon organization. These datasets are available in public repositories, such as the Gene Expression Omnibus, or ArrayExpress. However, accessing and navigating such a wealth of data is not straightforward. No resource currently exists that offers all available high and low-throughput data on transcriptional regulation in

Genomics has set the basis for a variety of methodologies that produce high-throughput datasets identifying the different players that define gene regulation, particularly regulation of transcription initiation and operon organization. These datasets are available in public repositories, such as the Gene Expression Omnibus, or ArrayExpress. However, accessing and navigating such a wealth of data is not straightforward. No resource currently exists that offers all available high and low-throughput data on transcriptional regulation in Escherichia coli K-12 to easily use both as whole datasets, or as individual interactions and regulatory elements. RegulonDB (https://regulondb.ccg.unam.mx) began gathering high-throughput dataset collections in 2009, starting with transcription start sites, then adding ChIP-seq and gSELEX in 2012, with up to 99 different experimental high-throughput datasets available in 2019. In this paper we present a radical upgrade to more than 2000 high-throughput datasets, processed to facilitate their comparison, introducing up-to-date collections of transcription termination sites, transcription units, as well as transcription factor binding interactions derived from ChIP-seq, ChIP-exo, gSELEX and DAP-seq experiments, besides expression profiles derived from RNA-seq experiments. For ChIP-seq experiments we offer both the data as presented by the authors, as well as data uniformly processed in-house, enhancing their comparability, as well as the traceability of the methods and reproducibility of the results. Furthermore, we have expanded the tools available for browsing and visualization across and within datasets. We include comparisons against previously existing knowledge in RegulonDB from classic experiments, a nucleotide-resolution genome viewer, and an interface that enables users to browse datasets by querying their metadata. A particular effort was made to automatically extract detailed experimental growth conditions by implementing an assisted curation strategy applying Natural language processing and machine learning. We provide summaries with the total number of interactions found in each experiment, as well as tools to identify common results among different experiments. This is a long-awaited resource to make use of such wealth of knowledge and advance our understanding of the biology of the model bacterium E. coli K-12.

Automatic document classification for highly interrelated classes is a demanding task that becomes more challenging when there is little labeled data for training. Such is the case of the coronavirus disease 2019 (COVID-19) Clinical repository—a repository of classified and translated academic articles related to COVID-19 and relevant to the clinical practice—where a 3-way classification scheme is being applied to COVID-19 literature. During the 7th Biomedical Linked Annotation Hackathon (BLAH7) hackathon, we performed experiments to explore the use of named-entity-recognition (NER) to improve the classification. We processed the literature with OntoGene’s Biomedical Entity Recogniser (OGER) and used the resulting identified Named Entities (NE) and their links to major biological databases as extra input features for the classifier. We compared the results with a baseline model without the OGER extracted features. In these proof-of-concept experiments, we observed a clear gain on COVID-19 literature classification. In particular, NE’s origin was useful to classify document types and NE’s type for clinical specialties. Due to the limitations of the small dataset, we can only conclude that our results suggests that NER would benefit this classification task. In order to accurately estimate this benefit, further experiments with a larger dataset would be needed.

The number of published papers in biomedical research makes it rather impossible for a researcher to keep up to date. This is where manually curated databases contribute facilitating the access to knowledge. However, the structure required by databases strongly limits the type of valuable information that can be incorporated. Here, we present Lisen&Curate, a curation system that facilitates linking sentences or part of sentences (both considered sources) in articles with their corresponding curated objects, so that rich additional information of these objects is easily available to users. These sources are going to be offered both within RegulonDB and a new database, L-Regulon. To show the relevance of our work, two senior curators performed a curation of 31 articles on the regulation of transcription initiation of E. coli using Lisen&Curate. As a result, 194 objects were curated and 781 sources were recorded. We also found that these sources are useful to develop automatic approaches to detect objects in articles by observing word frequency patterns and by carrying out an open information extraction task. Sources may help to elaborate a controlled vocabulary of experimental methods. Finally, we discuss our ecosystem of interconnected applications, RegulonDB, L-Regulon, and Lisen&Curate, to facilitate the access to knowledge on regulation of transcription initiation in bacteria. We see our proposal as the starting point to change the way experimentalists connect a piece of knowledge with its evidence using RegulonDB. This study was supported by the Universidad Nacional Autónoma de México (UNAM) and the National Institute of General Medical Sciences of the National Institutes of Health [grants number 5RO1-GM110597-04 and 1RO1-GM131643-01A1]

The amount of published papers in biomedical research makes it rather impossible for a researcher to keep up to date. This is where machine processing of scientific publications could contribute to facilitate the access to knowledge. How to make use of text mining capabilities and still preserve the high quality of manual curation, is the challenge we focused on. Here we present the Lisen&Curate system designed to enable current and future NLP capabilities within a curation environment interface used in curation of literature on the regulation of transcription initiation in bacteria. The current version extracts regulatory interactions with the corresponding sentences for curators to confirm or reject accelerating their curation. It also uses an embedded metrics of sentence similarity offering the curator an alternative mechanism of navigating through semantically similar sentences within a given paper as well as across papers of a pre-defined corpus of publications pertinent to the task. We show results of the use of the system to curate literature in E. coli as well as literature in Salmonella. A major advantage of the system is to save as part of the curation work, the precise link for every curated piece of knowledge with the corresponding specific sentence(s) in the curated publication supporting it. We discuss future directions of this type of curation infrastructure.

The analysis of genomic data has been used to generate information about genetic variants and expression patterns correlated with specific physical traits. In the last decades, these analyses have evolved toward analyzing thousands of entities at the same time. Moreover, these analyses have produced an enormous amount of biomedical literature reporting associations between genes and diseases. In this scenario, pattern recognition techniques have been truly useful, so a review of how these techniques have been applied is relevant. Thus, in this chapter we present a brief introduction to the high-throughput sequencing methodologies. Then, we describe the process of identification of genomic variants and genetic expression profiles that have been used for the diagnostic of diseases, followed by a general overview of the gene-disease association extraction from biomedical literature.

MotivationThe genetic mechanisms involved in human diseases are fundamental in biomedical research. Several databases with curated associations between genes and diseases have emerged in the last decades. Although, due to the demanding and time consuming nature of manual curation of literature, they still lack large amounts of information. Current automatic approaches extract associations by considering each abstract or sentence independently. This approach could potentially lead to contradictions between individual cases. Therefore, there is a current need for automatic strategies that can provide a literature consensus of gene-disease associations, and are not prone to making contradictory predictions.ResultsHere, we present GeDex, an effective and freely available automatic approach to extract consensus gene-disease associations from biomedical literature based on a predictive model trained with four simple features. As far as we know, it is the only system that reports a single consensus prediction from multiple sentences supporting the same association. We tested our approach on the curated fraction of DisGeNet (f-score 0.77) and validated it on a manually curated dataset, obtaining a competitive performance when compared to pre-existing methods (f-score 0.74). In addition, we effectively recovered associations from an article collection of chronic pulmonary diseases, and discovered that a large proportion is not reported in current databases. Our results demonstrate that GeDex, despite its simplicity, is a competitive tool that can successfully assist the curation of existing databases.AvailabilityGeDex is available at https://bitbucket.org/laigen/gedex/src/master/ and can be used as a docker image https://hub.docker.com/r/laigen/gedexContactcmendezc@ccg.unam.mxSupplementary informationSupplementary material are available at bioRxiv online.

RegulonDB, first published 20 years ago, is a comprehensive electronic resource about regulation of transcription initiation of Escherichia coli K-12 with decades of knowledge from classic molecular biology experiments, and recently also from high-throughput genomic methodologies. We curated the literature to keep RegulonDB up to date, and initiated curation of ChIP and gSELEX experiments. We estimate that current knowledge describes between 10% and 30% of the expected total number of transcription factor- gene regulatory interactions in E. coli. RegulonDB provides datasets for interactions for which there is no evidence that they affect expression, as well as expression datasets. We developed a proof of concept pipeline to merge binding and expression evidence to identify regulatory interactions. These datasets can be visualized in the RegulonDB JBrowse. We developed the Microbial Conditions Ontology with a controlled vocabulary for the minimal properties to reproduce an experiment, which contributes to integrate data from high throughput and classic literature. At a higher level of integration, we report Genetic Sensory-Response Units for 200 transcription factors, including their regulation at the metabolic level, and include summaries for 70 of them. Finally, we summarize our research with Natural language processing strategies to enhance our biocuration work.

This paper presents some experiments in the task of authorship attribution. We achieve this task by a stylometric analysis of some stylistic markers tested in two Spanish corpora. The first corpus is composed of long texts written by professional authors, while the second corpus is formed by short texts written by students. In both corpora, different text genres are included. Thus, the objective of this study is to analyze several stylometric variables to test its capacity as markers for authorship attribution when the corpora vary in size and text genre. We represent the texts as high dimensional vectors and we visualize the similarities between them using multidimensional scaling. We conclude that the length of texts is a factor that affects the discriminatory capacity of the stylometric variables. We also found that there are certain variables that are better than others to identify specific authors and specific text genres.

The RegulonDB (http://regulondb.ccg.unam.mx) team generates manually elaborated summaries about transcription factors (TFs) of Escherichia coli K-12. These texts involve considerable effort, since they summarize a diverse collection of structural, mechanistic and physiological properties of TFs and, due to constant new research, ideally they require frequent updating. In natural language processing, several techniques for automatic summarization have been developed. Therefore, our proposal is to extract, by using those techniques, relevant information about TFs for assisting the curation and elaboration of the manual summaries. Here, we present the results of the automatic classification of sentences about the biological processes regulated by a TF and the information about the structural domains constituting the TF. We tested two classical classifiers, Naïve Bayes and Support Vector Machines (SVMs), with the sentences of the manual summaries as training data. The best classifier was an SVM employing lexical, grammatical, and terminological features (F-score, 0.8689). The sentences of articles analyzed by this classifier were frequently true, but many sentences were set aside (high precision with low recall); consequently, some improvement is required. Nevertheless, automatic summaries of complete articles about five TFs, generated with this classifier, included much of the relevant information of the summaries written by curators (high ROUGE-1 recall). In fact, a manual comparison confirmed that the best summary encompassed 100% of the relevant information. Hence, our empirical results suggest that our proposal is promising for covering more properties of TFs to generate suggested sentences with relevant information to help the curation work without losing quality. Database URL RegulonDB, http://regulondb.ccg.unam.mx