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Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data

ABSTRACT: Accurate functional annotation of regulatory elements is essential for understanding global gene regulation. Here, we report a genome-wide map of 827,000 transcription factor binding sites in human lymphoblastoid cell lines, which is comprised of sites correspond-ing to 239 position weight matrices of known transcription factor binding motifs, and 49 novel sequence motifs. To generate this map, we developed a probabilistic framework that integrates cell- or tissue-speciﬁc experimental data such as histone modiﬁcations and DNa-seI cleavage patterns with genomic information such as gene annotation and evolutionary conservation. Comparison to empirical ChIP-seq data suggests that our method is highly accurate yet has the advantage of targeting many factors in a single assay. We anticipate that this approach will be a valuable tool for genome-wide studies of gene regulation in a wide variety of cell-types or tissues under diverse conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE25341 | GEO | 2010/11/15

SECONDARY ACCESSION(S): PRJNA134875

REPOSITORIES: GEO

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Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data

Project description:Accurate functional annotation of regulatory elements is essential for understanding global gene regulation. Here, we report a genome-wide map of 827,000 transcription factor binding sites in human lymphoblastoid cell lines, which is comprised of sites correspond-ing to 239 position weight matrices of known transcription factor binding motifs, and 49 novel sequence motifs. To generate this map, we developed a probabilistic framework that integrates cell- or tissue-speciﬁc experimental data such as histone modiﬁcations and DNa-seI cleavage patterns with genomic information such as gene annotation and evolutionary conservation. Comparison to empirical ChIP-seq data suggests that our method is highly accurate yet has the advantage of targeting many factors in a single assay. We anticipate that this approach will be a valuable tool for genome-wide studies of gene regulation in a wide variety of cell-types or tissues under diverse conditions. DNaseI-Seq on two YRI Hapmap cell lines. Each individual sequenced on 8 lanes of the Illumina Genome Analyzer II

2010-11-15 | E-GEOD-25341 | biostudies-arrayexpress

Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

Project description:The DNA sequence preferences of the vast majority of eukaryotic transcription factors (TFs) are unknown. Using an approach designed to broadly sample both DNA-binding domain types and eukaryotic clades, we have determined DNA-binding motifs for 1,033 TFs from 131 diverse eukaryotes, encompassing 54 domain types. Closely related orthologs and paralogs typically have very similar sequence preferences; this property allows inference of motifs for roughly one third of the 166,851 known or predicted eukaryotic TFs. While the origins of most motifs can be dated to hundreds of millions of years ago, we also characterize more recent TF expansions. Sequences matching the motifs are enriched upstream of TSS in most eukaryotic lineages, and at informative eQTL SNPs in Arabidopsis promoters, demonstrating their utility in mapping transcriptional networks. The motifs are housed at http://cisbp.ccbr.utoronto.ca Protein binding microarray (PBM) experiments were performed for a set of 1048 diverse eukaryotic transcription factors. Briefly, the PBMs involved binding GST-tagged DNA-binding proteins to two double-stranded 44K Agilent microarrays, each containing a different DeBruijn sequence design, in order to determine their sequence preferences. Details of the PBM protocol are described in Berger et al., Nature Biotechnology 2006.

2014-08-01 | E-GEOD-53348 | biostudies-arrayexpress

Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity

2014-08-01 | GSE53348 | GEO

Genome-wide transcription start site mapping of Bradyrhizobium japonicum free-living cells and bacteroids - a rich resource to identify new transcripts, proteins and to study gene regulation

Project description:Background: During the symbiosis with legumes, Bradyrhizobium japonicum cells infect roots where they induce the formation of root nodules and differentiate into intracellular nitrogen-fixing bacteroids. We used differential RNA-seq (dRNA-seq) for the genome-wide detection of transcriptional start sites (TSSs) in B. japonicum USDA 110 cells grown free-living or as bacteroids in soybean root nodules. Results: A newly developed TSS recognition procedure based on machine learning allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4,329 in bacteroids and 2,766 in both living conditions. Using a proteogenomics approach, we provide evidence for the translation of 107 new transcripts including 14 with TSSs in annotated genes. In addition, we provide evidence for 178 shorter or longer proteins, 109 of them with TSS support. Based on our TSS map and a new de novo promoter prediction algorithm, we identified promoter motifs mainly used in nodules (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). The data is made available in a generic feature format (GFF) file along with an updated and extended genome annotation comprising promoters, TSSs and terminators. The value of such a TSS and promoter map beyond the identification of novel transcripts and ORFs is illustrated by the experimental analysis of an antisense RNA, which is a by-product of transcriptional interference in a gene encoding a cytochrome P450 highly expressed in nodules. Conclusions: The genome-wide TSS and promoter map along with the extended genome annotation represents a very useful resource for detailed analyses of gene regulation and further systems biology studies on B. japonicum in symbiosis with soybean.

2016-04-18 | GSE69059 | GEO

Endogenous Linear Plasmids lp28-4 and lp25 are Required for Infectivity and Restriction Protection in the Lyme Disease Spirochete Borrelia mayonii

Project description:Single Molecule Real Time (SMRT) sequencing was utilized to map the genome-wide m6A methylation pattern in B. mayonii. Consensus modified motifs were identified in wildtype B. mayonii as well as clonal isolates lacking plasmids that encode predicted methyltransferases. Two conserved m6A modification motifs were identified, and were fully attributable to the presence of specific methyltransferases.

2023-02-13 | GSE220655 | GEO

Analysis of alternative cleavage and polyadenylation by 3' region extraction and deep sequencing

Project description:Alternative cleavage and polyadenylation (APA) generates diverse mRNA isoforms. We developed 3' region extraction and deep sequencing (3'READS) to address mispriming issues that commonly plague poly(A) site (pA) identification, and we used the method to comprehensively map pAs in the mouse genome. Thorough annotation of gene 3' ends revealed over 5,000 previously overlooked pAs (~8% of total) flanked by A-rich sequences, underscoring the necessity of using an accurate tool for pA mapping. About 79% of mRNA genes and 66% of long noncoding RNA genes undergo APA, but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Quantitative analysis of APA isoforms by 3'READS indicated that promoter-distal pAs, regardless of intron or exon locations, become more abundant during embryonic development and cell differentiation and that upregulated isoforms have stronger pAs, suggesting global modulation of the 3' endM-bM-^@M-^Sprocessing activity in development and differentiation. 3'READS to map pAs in mouse genome

2012-12-17 | E-GEOD-42398 | biostudies-arrayexpress

Utilizing HXMS to Uncover Structural Basis of CPC Phase Separation

Project description:The centromere is the locus that directs accurate chromosome segregation, and a mater regulatory complex ,the chromosome passenger comlex (CPC) is enriched in a region of the mitotic centromre termed the inner centromre. Recent findings support a role of CPC phase separation in its localization and function in mitotic error correction. Currently there are no teqhniques to globaly map the motifs on proteins that drive the multivalent interactions. In this context, we now employ hydrogen/deuterium exchange coupled to mass spectrometry (HXMS) to study dynamics of CPC phase separation.

2024-03-13 | PXD034374 | Pride

Accurate annotation of human protein-coding small open reading frames

Project description:Accurate annotation of human protein-coding small open reading frames

| PRJNA515538 | ENA

Genome annotation improvement of Brassica rapa

Project description:The mapping and functional analysis of quantitative traits in Brassica rapa can be greatly improved with the availability of physically positioned, gene-based genetic markers and accurate genome annotation. In this study, deep transcriptome RNA sequencing (RNA-Seq) of Brassica rapa was undertaken with two objectives: SNP detection and improved transcriptome annotation. We performed SNP detection on two varieties that are parents of a mapping population to aid in development of a marker system for this population and subsequent development of high-resolution genetic map. An improved Brassica rapa transcriptome was constructed to detect novel transcripts and to improve the current genome annotation. Deep RNA-Seq of two Brassica rapa genotypesâR500 (var. trilocularis, Yellow Sarson) and IMB211 (a rapid cycling variety)âusing eight different tissues (root, internode, leaf, petiole, apical meristem, floral meristem, silique, and seedling) grown across three different environments (growth chamber, greenhouse and field) and under two different treatments (simulated sun and simulated shade) generated 2.3 billion high-quality Illumina reads. In this experiment, two pools were made, with one pool consisting of 66 samples collected from growth chamber and another pool consisting of 60 samples collected from greenhouse and field. Each pool was sequenced on eight lanes (total 16 lanes) of an Illumina Genome Analyzer (GAIIx) as 100-bp paired end reads.

2014-04-22 | E-MTAB-4276 | biostudies-arrayexpress

De novo inference of thermodynamic binding energies using deep learning models of in vivo transcription factor binding

Project description:We introduce Affinity Distillation (AD), a method for extracting thermodynamic affinities de-novo from in-vivo immunoprecipitation experiments using deep learning. We show that neural networks modeling base-resolution in-vivo binding profiles of yeast and mammalian TFs can accurately predict energetic impacts of varying underlying DNA sequence on TF binding. Systematic comparisons between Affinity Distillation predictions and other predictive algorithms consistently show that Affinity Distillation more accurately predicts affinities across a wide range of TF structural classes and DNA sequences. Affinity Distillation relies on in-silico marginalization against many sequence backgrounds, resulting in a higher dynamic range and more accurate predictions than motif discovery algorithms. Moreover, we show that Affinity Distillation can learn differential paralog-specific affinities, thereby making it possible to more accurately reconstruct regulatory networks in cells.

2022-06-29 | GSE207001 | GEO

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