XSTREME: Comprehensive motif analysis of biological sequence datasets

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Sept. 3, 2021

Abstract XSTREME is a web-based tool for performing comprehensive motif discovery and analysis in DNA, RNA or protein sequences, as well sequences user-defined alphabets. It designed both very large small datasets. similar to the MEME-ChIP tool, but expands upon its capabilities several ways. Like MEME-ChIP, performs two types of de novo discovery, also enrichment input using databases known motifs. Unlike which ranks motifs based on their centers uses anywhere this purpose. Consequently, more appropriate motif-based regardless how are distributed within sequences. MEME STREME algorithms recently developed SEA algorithm analysis. The interactive HTML output produced by includes highly accurate significance estimates, plots positional distribution each motif, histograms number matches easy use via web server at https://meme-suite.org , fully integrated with widely-used Suite sequence tools, can be freely downloaded same site non-commercial use.

Language: Английский

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iDNA-ABF: multi-scale deep biological language learning model for the interpretable prediction of DNA methylations

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: Oct. 17, 2022

Abstract In this study, we propose iDNA-ABF, a multi-scale deep biological language learning model that enables the interpretable prediction of DNA methylations based on genomic sequences only. Benchmarking comparisons show our iDNA-ABF outperforms state-of-the-art methods for different methylation predictions. Importantly, power in capturing both sequential and functional semantics information from background genomes. Moreover, by integrating analysis mechanism, well explain what learns, helping us build mapping discovery important determinants to in-depth their functions.

Language: Английский

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Mammalian evolution of human cis-regulatory elements and transcription factor binding sites

Science, Journal Year: 2023, Volume and Issue: 380(6643)

Published: April 27, 2023

Understanding the regulatory landscape of human genome is a long-standing objective modern biology. Using reference-free alignment across 241 mammalian genomes produced by Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million candidate cis-regulatory elements (cCREs) and 15.6 transcription factor binding sites (TFBSs). We identified 439,461 cCREs 2,024,062 TFBSs under constraint. Genes near constrained perform fundamental cellular processes, whereas genes primate-specific are involved in environmental interaction, including odor perception immune response. About 20% transposable element-derived exhibit intricate patterns gains losses during primate evolution sequence variants associated with complex traits enriched TFBSs. Our annotations illuminate functions genome.

Language: Английский

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Massively parallel characterization of transcriptional regulatory elements in three diverse human cell types

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 6, 2023

ABSTRACT The human genome contains millions of candidate cis -regulatory elements (CREs) with cell-type-specific activities that shape both health and myriad disease states. However, we lack a functional understanding the sequence features control activity these CREs. Here, used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test regulatory over 680,000 sequences, representing nearly comprehensive set all annotated CREs among three cell types (HepG2, K562, WTC11), finding 41.7% be functional. By testing sequences in orientations, find promoters have significant strand orientation effects. We also observe their 200 nucleotide cores function as non-cell-type-specific ‘on switches’ providing similar expression levels associated gene. In contrast, enhancers weaker effects, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, develop sequence-based models predict CRE high accuracy delineate motifs. Testing an additional library encompassing 60,000 types, further identified factors determine cell-type specificity. Collectively, work provides exhaustive catalog widely lines, showcases how large-scale measurements can dissect grammar.

Language: Английский

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DNA-guided transcription factor cooperativity shapes face and limb mesenchyme

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 692 - 711.e26

Published: Jan. 22, 2024

Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest that it may be common, examples of such cooperativity remain scarce contexts. Here, we demonstrate how "Coordinator," a long DNA motif composed common motifs bound by many basic helix-loop-helix (bHLH) and homeodomain (HD) TFs, uniquely defines the regions embryonic face limb mesenchyme. Coordinator guides cooperative selective binding between bHLH family mesenchymal regulator TWIST1 collective HD associated with regional limb. required open chromatin at sites, whereas stabilize occupancy titrate away from HD-independent sites. This results shared regulation genes involved cell-type positional ultimately shapes facial morphology evolution.

Language: Английский

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Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features

Science, Journal Year: 2024, Volume and Issue: 383(6685)

Published: Feb. 22, 2024

In some mammals, notably humans, recombination occurs almost exclusively where the protein PRDM9 binds, whereas in vertebrates lacking an intact

Language: Английский

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DDX3 depletion represses translation of mRNAs with complex 5′ UTRs

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(9), P. 5336 - 5350

Published: April 9, 2021

Abstract DDX3 is an RNA chaperone of the DEAD-box family that regulates translation. Ded1, yeast ortholog DDX3, a global regulator translation, whereas thought to preferentially affect subset mRNAs. However, set mRNAs are regulated by unknown, along with relationship between binding and activity. Here, we use ribosome profiling, RNA-seq, PAR-CLIP define in human cells. We find while binds highly expressed mRNAs, depletion particularly affects translation small transcriptome. further site on helix 16 ribosomal rRNA, placing it immediately adjacent mRNA entry channel. Translation changes caused depleting levels or expressing inactive point mutation different, consistent different association these genetic variant types disease. Taken together, this work defines transcriptome responsive inhibition, relevance for basic biology disease states where altered.

Language: Английский

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Attention-based multi-label neural networks for integrated prediction and interpretation of twelve widely occurring RNA modifications

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 29, 2021

Abstract Recent studies suggest that epi-transcriptome regulation via post-transcriptional RNA modifications is vital for all types. Precise identification of modification sites essential understanding the functions and regulatory mechanisms RNAs. Here, we present MultiRM, a method integrated prediction interpretation from sequences. Built upon an attention-based multi-label deep learning framework, MultiRM not only simultaneously predicts putative twelve widely occurring transcriptome (m 6 A, m 1 5 C, U, Am, 7 G, Ψ, I, Cm, Gm, Um), but also returns key sequence contents contribute most to positive predictions. Importantly, our model revealed strong association among different types perspective their associated contexts. Our work provides solution detecting multiple modifications, enabling analysis these gaining better sequence-based mechanisms.

Language: Английский

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A test of the pioneer factor hypothesis using ectopic liver gene activation

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 5, 2022

The pioneer factor hypothesis (PFH) states that factors (PFs) are a subclass of transcription (TFs) bind to and open inaccessible sites then recruit non-pioneer (non-PFs) activate batteries silent genes. PFH predicts ectopic gene activation requires the sequential activity qualitatively different TFs. We tested by expressing endodermal PF FOXA1 non-PF HNF4A in K562 lymphoblast cells. While co-expression activated burst endoderm-specific expression, we found no evidence for functional distinction between these two When expressed independently, both TFs bound opened sites, genes, ‘pioneered’ each other, although required fewer copies its motif binding. A subset targets TFs, but predominant mode action at did not conform predicted PFH. From results, hypothesize an alternative where ‘pioneer activity’ depends on categorically rather affinity interaction TF DNA.

Language: Английский

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Insights into the biosynthesis pathway of phenolic compounds in microalgae

Computational and Structural Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20, P. 1901 - 1913

Published: Jan. 1, 2022

Among the most relevant bioactive molecules family, phenolic compounds (PCs) are well known in higher plants, while their knowledge microalgae is still scarce. Microalgae represent a novel and promising source of human health benefit to be involved, for instance, nutraceutical composition. This study aims investigate PCs biosynthetic pathway microalgal realm, exploring its potential variability over biodiversity axis. A multistep silico analysis was carried out using selection core enzymes from described land plants. explores presence ten groups prokaryotic eukaryotic microalgae.. Analyses were taking into account wide algal protein homologs, functional annotation conserved domains motifs, maximum-likelihood tree construction. Results showed that biosynthesis shared horizontally all microalgae. Conversely, ability synthesize some subclasses phenolics may restricted only (i.e., Chlorophyta) depending on featured enzymes, such as flavanone naringenin other related chalcone isomerase dependent compounds.

Language: Английский

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