Predictive Biophysical Neural Network Modeling of a Compendium of Transcription Factor DNA Binding Profiles for .

The DNA binding of most Transcription Factors (TFs) has not been comprehensively mapped, and few have models that can quantitatively predict binding affinity. We report the global mapping of DNA binding for 139 TFs using ChIP-Seq. We used these data to train BoltzNet, a novel neural network that predicts TF binding energy from DNA sequence.

Flexible gold standards for transcription factor regulatory interactions in K-12: architecture of evidence types.

Post-genomic implementations have expanded the experimental strategies to identify elements involved in the regulation of transcription initiation. Here, we present for the first time a detailed analysis of the sources of knowledge supporting the collection of transcriptional regulatory interactions (RIs) of K-12. An RI groups the transcription factor, its effect (positive or negative) and the regulated target, a promoter, a gene or transcription unit.

RegulonDB v12.0: a comprehensive resource of transcriptional regulation in E. coli K-12.

RegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements.

The EcoCyc Database (2023).

EcoCyc is a bioinformatics database available online at EcoCyc.org that describes the genome and the biochemical machinery of K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of .

A Gold Standard for Transcription Factor Regulatory Interactions in K-12: Architecture of Evidence Types.

Post-genomic implementations have expanded the experimental strategies to identify elements involved in the regulation of transcription initiation. As new methodologies emerge, a natural step is to compare their results with those from established methodologies, such as the classic methods of molecular biology used to characterize transcription factor binding sites, promoters, or transcription units. In the case of K-12, the best-studied microorganism, for the last 30 years we have continuously gathered such knowledge from original scientific publications, and have organized it in two databases, RegulonDB and EcoCyc.

RegulonDB 11.0: Comprehensive high-throughput datasets on transcriptional regulation in K-12.

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.

Missing Links Between Gene Function and Physiology in Genomics.

Knowledge of biological organisms at the molecular level that has been gathered is now organized into databases, often within ontological frameworks. To enable computational comparisons of annotations across different genomes and organisms, controlled vocabularies have been essential, as is the case in the functional annotation classifications used for bacteria, such as MultiFun and the more widely used Gene Ontology. The function of individual gene products as well as the processes in which collections of them participate constitute a wealth of classes that describe the biological role of gene products in a large number of organisms in the three kingdoms of life.

Sensory Systems and Transcriptional Regulation in .

In free-living bacteria, the ability to regulate gene expression is at the core of adapting and interacting with the environment. For these systems to have a logic, a signal must trigger a genetic change that helps the cell to deal with what implies its presence in the environment; briefly, the response is expected to include a feedback to the signal. Thus, it makes sense to think of genetic sensory mechanisms of gene regulation.

Lisen&Curate: A platform to facilitate gathering textual evidence for curation of regulation of transcription initiation in bacteria.

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.

The EcoCyc Database in 2021.

The EcoCyc model-organism database collects and summarizes experimental data for K-12. EcoCyc is regularly updated by the manual curation of individual database entries, such as genes, proteins, and metabolic pathways, and by the programmatic addition of results from select high-throughput analyses. Updates to the Pathway Tools software that supports EcoCyc and to the web interface that enables user access have continuously improved its usability and expanded its functionality.

Knowledge extraction for assisted curation of summaries of bacterial transcription factor properties.

Transcription factors (TFs) play a main role in transcriptional regulation of bacteria, as they regulate transcription of the genetic information encoded in DNA. Thus, the curation of the properties of these regulatory proteins is essential for a better understanding of transcriptional regulation. However, traditional manual curation of article collections to compile descriptions of TF properties takes significant time and effort due to the overwhelming amount of biomedical literature, which increases every day.

Redefining fundamental concepts of transcription initiation in bacteria.

Despite enormous progress in understanding the fundamentals of bacterial gene regulation, our knowledge remains limited when compared with the number of bacterial genomes and regulatory systems to be discovered. Derived from a small number of initial studies, classic definitions for concepts of gene regulation have evolved as the number of characterized promoters has increased. Together with discoveries made using new technologies, this knowledge has led to revised generalizations and principles.

PulmonDB: a curated lung disease gene expression database.

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) have contrasting clinical and pathological characteristics and interesting whole-genome transcriptomic profiles. However, data from public repositories are difficult to reprocess and reanalyze. Here, we present PulmonDB, a web-based database (http://pulmondb.

Limits to a classic paradigm: most transcription factors in E. coli regulate genes involved in multiple biological processes.

Transcription factors (TFs) are important drivers of cellular decision-making. When bacteria encounter a change in the environment, TFs alter the expression of a defined set of genes in order to adequately respond. It is commonly assumed that genes regulated by the same TF are involved in the same biological process.

Similarity corpus on microbial transcriptional regulation.

Background: The ability to express the same meaning in different ways is a well-known property of natural language. This amazing property is the source of major difficulties in natural language processing. Given the constant increase in published literature, its curation and information extraction would strongly benefit from efficient automatic processes, for which corpora of sentences evaluated by experts are a valuable resource.

Integrating Bacterial ChIP-seq and RNA-seq Data With SnakeChunks.

Next-generation sequencing (NGS) is becoming a routine approach in most domains of the life sciences. To ensure reproducibility of results, there is a crucial need to improve the automation of NGS data processing and enable forthcoming studies relying on big datasets. Although user-friendly interfaces now exist, there remains a strong need for accessible solutions that allow experimental biologists to analyze and explore their results in an autonomous and flexible way.

The EcoCyc Database.

EcoCyc is a bioinformatics database available at EcoCyc.org that describes the genome and the biochemical machinery of K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of .

A unified resource for transcriptional regulation in Escherichia coli K-12 incorporating high-throughput-generated binding data into RegulonDB version 10.0.

Background: Our understanding of the regulation of gene expression has benefited from the availability of high-throughput technologies that interrogate the whole genome for the binding of specific transcription factors and gene expression profiles. In the case of widely used model organisms, such as Escherichia coli K-12, the new knowledge gained from these approaches needs to be integrated with the legacy of accumulated knowledge from genetic and molecular biology experiments conducted in the pre-genomic era in order to attain the deepest level of understanding possible based on the available data.

Results: In this paper, we describe an expansion of RegulonDB, the database containing the rich legacy of decades of classic molecular biology experiments supporting what we know about gene regulation and operon organization in E.

Using RegulonDB, the Escherichia coli K-12 Gene Regulatory Transcriptional Network Database.

In RegulonDB, for over 25 years, we have been gathering knowledge by manual curation from original scientific literature on the regulation of transcription initiation and genome organization in transcription units of the Escherichia coli K-12 genome. This unit describes six basic protocols that can serve as a guiding introduction to the main content of the current version (v9.4) of this electronic resource.

First steps in automatic summarization of transcription factor properties for RegulonDB: classification of sentences about structural domains and regulated processes.

RegulonDB, http://regulondb.ccg.unam.

Genome-Wide Mapping of Transcriptional Regulation and Metabolism Describes Information-Processing Units in .

In the face of changes in their environment, bacteria adjust gene expression levels and produce appropriate responses. The individual layers of this process have been widely studied: the transcriptional regulatory network describes the regulatory interactions that produce changes in the metabolic network, both of which are coordinated by the signaling network, but the interplay between them has never been described in a systematic fashion. Here, we formalize the process of detection and processing of environmental information mediated by individual transcription factors (TFs), utilizing a concept termed genetic sensory response units (GENSOR units), which are composed of four components: (1) a signal, (2) signal transduction, (3) genetic switch, and (4) a response.

Improving biocuration of microRNAs in diseases: a case study in idiopathic pulmonary fibrosis.

Unlabelled: MicroRNAs (miRNAs) are small and non-coding RNA molecules that inhibit gene expression posttranscriptionally. They play important roles in several biological processes, and in recent years there has been an interest in studying how they are related to the pathogenesis of diseases. Although there are already some databases that contain information for miRNAs and their relation with illnesses, their curation represents a significant challenge due to the amount of information that is being generated every day.