BMC Med. 2024 Jul 18;22(1):294. doi: 10.1186/s12916-024-03503-y.

ABSTRACT

BACKGROUND: Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case-control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease.

METHODS: A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes' sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis.

RESULTS: Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 < 0.0007, p-values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes' sequence reads were not significantly different between groups (all FDR p-values > 0.05).

CONCLUSIONS: Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.

PMID:39020289 | DOI:10.1186/s12916-024-03503-y

Physiol Plant. 2024 Jul-Aug;176(4):e14441. doi: 10.1111/ppl.14441.

ABSTRACT

Approximately 60% of the genes and gene products in the model species Arabidopsis thaliana have been functionally characterized. In non-model plant species, the functional annotation of the gene space is largely based on homology, with the assumption that genes with shared common ancestry have conserved functions. However, the wide variety in possible morphological, physiological, and ecological differences between plant species gives rise to many species- and clade-specific genes, for which this transfer of knowledge is not possible. Other complications, such as difficulties with genetic transformation, the absence of large-scale mutagenesis methods, and long generation times, further lead to the slow characterization of genes in non-model species. Here, we discuss different resources that integrate plant gene function information. Different approaches that support the functional annotation of gene products, based on orthology or network biology, are described. While sequence-based tools to characterize the functional landscape in non-model species are maturing and becoming more readily available, easy-to-use network-based methods inferring plant gene functions are not as prevalent and have limited functionality.

PMID:39019770 | DOI:10.1111/ppl.14441

Sci Adv. 2024 Jul 19;10(29):eadl5638. doi: 10.1126/sciadv.adl5638. Epub 2024 Jul 17.

ABSTRACT

Viruses can selectively repress the translation of mRNAs involved in the antiviral response. RNA viruses exploit the Grb10-interacting GYF (glycine-tyrosine-phenylalanine) proteins 2 (GIGYF2) and eukaryotic translation initiation factor 4E (eIF4E) homologous protein 4EHP to selectively repress the translation of transcripts such as Ifnb1, which encodes the antiviral cytokine interferon-β (IFN-β). Herein, we reveal that GIGYF1, a paralog of GIGYF2, robustly represses cellular mRNA translation through a distinct 4EHP-independent mechanism. Upon recruitment to a target mRNA, GIGYF1 binds to subunits of eukaryotic translation initiation factor 3 (eIF3) at the eIF3-eIF4G1 interaction interface. This interaction disrupts the eIF3 binding to eIF4G1, resulting in transcript-specific translational repression. Depletion of GIGYF1 induces a robust immune response by derepressing IFN-β production. Our study highlights a unique mechanism of translational regulation by GIGYF1 that involves sequestering eIF3 and abrogating its binding to eIF4G1. This mechanism has profound implications for the host response to viral infections.

PMID:39018414 | DOI:10.1126/sciadv.adl5638

Sci Adv. 2024 Jul 19;10(29):eado2957. doi: 10.1126/sciadv.ado2957. Epub 2024 Jul 17.

ABSTRACT

Enzymatic cleavage of C─F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of α, β-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. The microbial defluorination products were structurally confirmed and showed regiospecificity and stereospecificity, consistent with their formation by enzymatic reactions. A comparison of defluorination activities among several Acetobacterium species indicated that a functional fluoride exporter was required for the detoxification of the released fluoride. Results from both in vivo inhibition tests and in silico enzyme modeling suggested the involvement of enzymes of the flavin-based electron-bifurcating caffeate reduction pathway [caffeoyl-CoA reductase (CarABCDE)] in the reductive defluorination. This is a report on specific microorganisms carrying out enzymatic reductive defluorination of PFAS, which could be linked to electron-bifurcating reductases that are environmentally widespread.

PMID:39018407 | DOI:10.1126/sciadv.ado2957

Sci Adv. 2024 Jul 19;10(29):eado2623. doi: 10.1126/sciadv.ado2623. Epub 2024 Jul 17.

ABSTRACT

Diatoms are major players in the global carbon cycle, and their metabolism is affected by ocean conditions. Understanding the impact of changing inorganic nutrients in the oceans on diatoms is crucial, given the changes in global carbon dioxide levels. Here, we present a genome-scale metabolic model (iMK1961) for Cylindrotheca closterium, an in silico resource to understand uncharacterized metabolic functions in this ubiquitous diatom. iMK1961 represents the largest diatom metabolic model to date, comprising 1961 open reading frames and 6718 reactions. With iMK1961, we identified the metabolic response signature to cope with drastic changes in growth conditions. Comparing model predictions with Tara Oceans transcriptomics data unraveled C. closterium's metabolism in situ. Unexpectedly, the diatom only grows photoautotrophically in 21% of the sunlit ocean samples, while the majority of the samples indicate a mixotrophic (71%) or, in some cases, even a heterotrophic (8%) lifestyle in the light. Our findings highlight C. closterium's metabolic flexibility and its potential role in global carbon cycling.

PMID:39018398 | DOI:10.1126/sciadv.ado2623

Sci Adv. 2024 Jul 19;10(29):eadn4582. doi: 10.1126/sciadv.adn4582. Epub 2024 Jul 17.

ABSTRACT

The pyruvate dehydrogenase complex (PDHc) is a key megaenzyme linking glycolysis with the citric acid cycle. In mammalian PDHc, dihydrolipoamide acetyltransferase (E2) and the dihydrolipoamide dehydrogenase-binding protein (E3BP) form a 60-subunit core that associates with the peripheral subunits pyruvate dehydrogenase (E1) and dihydrolipoamide dehydrogenase (E3). The structure and stoichiometry of the fully assembled, mammalian PDHc or its core remained elusive. Here, we demonstrate that the human PDHc core is formed by 48 E2 copies that bind 48 E1 heterotetramers and 12 E3BP copies that bind 12 E3 homodimers. Cryo-electron microscopy, together with native and cross-linking mass spectrometry, confirmed a core model in which 8 E2 homotrimers and 12 E2-E2-E3BP heterotrimers assemble into a pseudoicosahedral particle such that the 12 E3BP molecules form six E3BP-E3BP intertrimer interfaces distributed tetrahedrally within the 60-subunit core. The even distribution of E3 subunits in the peripheral shell of PDHc guarantees maximum enzymatic activity of the megaenzyme.

PMID:39018392 | DOI:10.1126/sciadv.adn4582

Photosynth Res. 2024 Jul 17. doi: 10.1007/s11120-024-01103-8. Online ahead of print.

ABSTRACT

Low iron (Fe) bioavailability can limit the biosynthesis of Fe-containing proteins, which are especially abundant in photosynthetic organisms, thus negatively affecting global primary productivity. Understanding cellular coping mechanisms under Fe limitation is therefore of great interest. We surveyed the temporal responses of Chlamydomonas (Chlamydomonas reinhardtii) cells transitioning from an Fe-rich to an Fe-free medium to document their short and long-term adjustments. While slower growth, chlorosis and lower photosynthetic parameters are evident only after one or more days in Fe-free medium, the abundance of some transcripts, such as those for genes encoding transporters and enzymes involved in Fe assimilation, change within minutes, before changes in intracellular Fe content are noticeable, suggestive of a sensitive mechanism for sensing Fe. Promoter reporter constructs indicate a transcriptional component to this immediate primary response. With acetate provided as a source of reduced carbon, transcripts encoding respiratory components are maintained relative to transcripts encoding components of photosynthesis and tetrapyrrole biosynthesis, indicating metabolic prioritization of respiration over photosynthesis. In contrast to the loss of chlorophyll, carotenoid content is maintained under Fe limitation despite a decrease in the transcripts for carotenoid biosynthesis genes, indicating carotenoid stability. These changes occur more slowly, only after the intracellular Fe quota responds, indicating a phased response in Chlamydomonas, involving both primary and secondary responses during acclimation to poor Fe nutrition.

PMID:39017982 | DOI:10.1007/s11120-024-01103-8

Curr Microbiol. 2024 Jul 17;81(9):273. doi: 10.1007/s00284-024-03791-w.

ABSTRACT

In pharmaceutical manufacturing, ensuring product safety involves the detection and identification of microorganisms with human pathogenic potential, including Burkholderia cepacia complex (BCC), Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Clostridium sporogenes, Candida albicans, and Mycoplasma spp., some of which may be missed or not identified by traditional culture-dependent methods. In this study, we employed a metagenomic approach to detect these taxa, avoiding the limitations of conventional cultivation methods. We assessed the groundwater microbiome's taxonomic and functional features from samples collected at two locations in the spring and summer. All datasets comprised 436-557 genera with Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Cyanobacteria accounting for > 95% of microbial DNA sequences. The aforementioned species constituted less than 18.3% of relative abundance. Escherichia and Salmonella were mainly detected in Hot Springs, relative to Jefferson, while Clostridium and Pseudomonas were mainly found in Jefferson relative to Hot Springs. Multidrug resistance efflux pumps and BlaR1 family regulatory sensor-transducer disambiguation dominated in Hot Springs and in Jefferson. These initial results provide insight into the detection of specified microorganisms and could constitute a framework for the establishment of comprehensive metagenomic analysis for the microbiological evaluation of pharmaceutical-grade water and other non-sterile pharmaceutical products, ensuring public safety.

PMID:39017960 | DOI:10.1007/s00284-024-03791-w

J Cell Sci. 2024 Jul 17:jcs.262343. doi: 10.1242/jcs.262343. Online ahead of print.

ABSTRACT

Neurofibromatosis type 1, a genetic disorder caused by germline mutations in NF1, predisposes patients to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas, and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors such as glioblastoma (GBM), melanoma, breast, ovarian, and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy, and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified the BORC complex, which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC complex subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that the BORC complex may be a promising therapeutic target for NF1-deficient tumors.

PMID:39016685 | DOI:10.1242/jcs.262343

Postepy Biochem. 2024 May 23;70(1):88-94. doi: 10.18388/pb.2021_520. Print 2024 May 23.

ABSTRACT

Information coded in DNA is replicated, modified and transmitted from the origins of protein-based life. Analogies of these processes to information processing, transmission and storage in computer systems is straightforward and can be utilized both in analysis of biological data and in development of biologically based technical systems. Transcription and translation processes are regulated by extremely complex regulatory networks, providing control of cell growth, cell cycle and cellular responses to stress. As such, they constitute engineering control systems exerting their actions at many levels of time scale and spatial organization. This work presents an engineering perspective on DNA-related information processing and biochemical process control in living cells, followed by a review of two-way crosstalk between engineering and biology.

PMID:39016228 | DOI:10.18388/pb.2021_520

Postepy Biochem. 2024 May 23;70(1):100-107. doi: 10.18388/pb.2021_525. Print 2024 May 23.

ABSTRACT

This essay is in memoriam of Professor Mieczysław Chorąży (1925 - 2021). Eminent Man, outstanding scientist, soldier of the Warsaw Uprising, moral authority for generations of fellow researchers and an exceptionally warm person. His character and life works are recalled here against the background of the times he lived in.

PMID:39016226 | DOI:10.18388/pb.2021_525

Postepy Biochem. 2024 May 23;70(1):1-3. doi: 10.18388/pb.2021_545. Print 2024 May 23.

ABSTRACT

Wonderful World of Nucleic Acids.

PMID:39016221 | DOI:10.18388/pb.2021_545

Front Physiol. 2024 Jul 2;15:1394740. doi: 10.3389/fphys.2024.1394740. eCollection 2024.

ABSTRACT

Ischemic stroke, a significant threat to human life and health, refers to a class of conditions where brain tissue damage is induced following decreased cerebral blood flow. The incidence of ischemic stroke has been steadily increasing globally, and its disease mechanisms are highly complex and involve a multitude of biological mechanisms at various scales from genes all the way to the human body system that can affect the stroke onset, progression, treatment, and prognosis. To complement conventional experimental research methods, computational systems biology modeling can integrate and describe the pathogenic mechanisms of ischemic stroke across multiple biological scales and help identify emergent modulatory principles that drive disease progression and recovery. In addition, by running virtual experiments and trials in computers, these models can efficiently predict and evaluate outcomes of different treatment methods and thereby assist clinical decision-making. In this review, we summarize the current research and application of systems-level computational modeling in the field of ischemic stroke from the multiscale mechanism-based, physics-based and omics-based perspectives and discuss how modeling-driven research frameworks can deliver insights for future stroke research and drug development.

PMID:39015225 | PMC:PMC11250596 | DOI:10.3389/fphys.2024.1394740

iScience. 2024 Jun 11;27(7):110241. doi: 10.1016/j.isci.2024.110241. eCollection 2024 Jul 19.

ABSTRACT

Adult stem cells play a critical role in tissue repair and maintenance. In tissues with slow turnover, including skeletal muscle, these cells are maintained in a mitotically quiescent state yet remain poised to re-enter the cell cycle to replenish themselves and regenerate the tissue. Using a panomics approach we show that the PAX7/NEDD4L axis acts against muscle stem cell activation in homeostatic skeletal muscle. Our findings suggest that PAX7 transcriptionally activates the E3 ubiquitin ligase Nedd4L and that the conditional genetic deletion of Nedd4L impairs muscle stem cell quiescence, with an upregulation of cell cycle and myogenic differentiation genes. Loss of Nedd4L in muscle stem cells results in the expression of doublecortin (DCX), which is exclusively expressed during their in vivo activation. Together, these data establish that the ubiquitin proteasome system, mediated by Nedd4L, is a key contributor to the muscle stem cell quiescent state in adult mice.

PMID:39015146 | PMC:PMC11250905 | DOI:10.1016/j.isci.2024.110241

New Phytol. 2024 Jul 16. doi: 10.1111/nph.19964. Online ahead of print.

ABSTRACT

Phytohormones possess unique chemical structures, and their physiological effects are regulated through intricate interactions or crosstalk among multiple phytohormones. MALDI-MSI enables the simultaneous detection and imaging of multiple hormones. However, its application for tracing phytohormones is currently restricted by low abundance of hormone in plant and suboptimal matrix selection. 2,4-Dihydroxy-5-nitrobenzoic acid (DHNBA) was reported as a new MALDI matrix for the enhanced detection and imaging of multiple phytohormones in plant tissues. DHNBA demonstrates remarkable sensitivity improvement when compared to the commonly used matrix, 2,5-dihydroxybenzoic acid (DHB), in the detection of isoprenoid cytokinins (trans-zeatin (tZ), dihy-drozeatin (DHZ), meta-topolin (mT), and N6-(Δ2-isopentenyl) adenine (iP)), jasmonic acid (JA), abscisic acid (ABA), and 1-aminocyclo-propane-1-carboxylic acid (ACC) standards. The distinctive properties of DHNBA (i.e. robust UV absorption, uniform matrix deposition, negligible background interference, and high ionization efficiency of phytohormones) make it as an ideal matrix for enhanced detection and imaging of phytohormones, including tZ, DHZ, ABA, indole-3-acetic acid (IAA), and ACC, by MALDI-MSI in various plant tissues, for example germinating seeds, primary/lateral roots, and nodules. Employing DHNBA significantly enhances our capability to concurrently track complex phytohormone biosynthesis pathways while providing precise differentiation of the specific roles played by individual phytohormones within the same category. This will propel forward the comprehensive exploration of phytohormonal functions in plant science.

PMID:39014531 | DOI:10.1111/nph.19964

J Ind Microbiol Biotechnol. 2024 Jul 16:kuae026. doi: 10.1093/jimb/kuae026. Online ahead of print.

ABSTRACT

The industrial amino acid production workhorse, Corynebacterium glutamicum naturally produces low levels of 2,3,5,6-tetramethylpyrazine (TMP), a valuable flavor, fragrance and commodity chemical. Here we demonstrate TMP production (∼0.8 ​g L-1) in C. glutamicum type strain ATCC13032 via overexpression of acetolactate synthase and/or alpha-acetolactate decarboxylase from Lactococcus lactis in CGXII minimal medium supplemented with 40 g L-1 glucose. This engineered strain also demonstrated growth and TMP production when the minimal medium was supplemented with up to 40% (v v-1) hydrolysates derived from ionic liquid pretreated sorghum biomass. A key objective was to take the fully engineered strain developed in this study and interrogate media parameters that influence the production of TMP, a critical post strain engineering optimization. Design of experiments in a high throughput plate format identified glucose, urea and their ratio as significant components affecting TMP production. These two components were further optimized using response surface methodology. In the optimized CGXII medium, the engineered strain could produce up to 3.56 g L-1 TMP (4-fold enhancement in titers and 2-fold enhancement in yield, mol mol-1) from 80 g L-1 glucose and 11.9 g L-1 urea in shake flask batch cultivation.

PMID:39013608 | DOI:10.1093/jimb/kuae026

Cell Host Microbe. 2024 Jul 10:S1931-3128(24)00231-2. doi: 10.1016/j.chom.2024.06.013. Online ahead of print.

ABSTRACT

Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting the mitochondrial chaperone, heat shock protein 60 (Hsp60Δ/ΔIEC). This metabolic perturbation causes self-resolving tissue injury. Regeneration is disrupted in the absence of the aryl hydrocarbon receptor (Hsp60Δ/ΔIEC;AhR-/-) involved in intestinal homeostasis or inflammatory regulator interleukin (IL)-10 (Hsp60Δ/ΔIEC;Il10-/-), causing IBD-like pathology. Injury is absent in the distal colon of germ-free (GF) Hsp60Δ/ΔIEC mice, highlighting bacterial control of metabolic injury. Colonizing GF Hsp60Δ/ΔIEC mice with the synthetic community OMM12 reveals expansion of metabolically flexible Bacteroides, and B. caecimuris mono-colonization recapitulates the injury. Transcriptional profiling of the metabolically impaired epithelium reveals gene signatures involved in oxidative stress (Ido1, Nos2, Duox2). These signatures are observed in samples from Crohn's disease patients, distinguishing active from inactive inflammation. Thus, mitochondrial perturbation of the epithelium causes microbiota-dependent injury with discriminative inflammatory gene profiles relevant for IBD.

PMID:39013472 | DOI:10.1016/j.chom.2024.06.013

Nat Med. 2024 Jul 16. doi: 10.1038/s41591-024-03189-y. Online ahead of print.

ABSTRACT

Global emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses, and their transmission to dairy cattle and animals, including humans, pose a significant global public health threat. Therefore, development of effective vaccines and therapeutics against H5N1 clade 2.3.4.4b virus is considered a public health priority. In the U.S., three H5N1 vaccines derived from earlier strains of HPAI H5N1 (A/Vietnam; clade 1 and A/Indonesia; clade 2.1) virus, with (MF59 or AS03) or without adjuvants, are licensed and stockpiled for pre-pandemic preparedness, but whether they can elicit neutralizing antibodies against circulating H5N1 clade 2.3.4.4b viruses is unknown. In this study, we evaluated the binding, hemagglutination inhibition and neutralizing antibody response generated following vaccination of adults with the three licensed vaccines. Individuals vaccinated with the two adjuvanted licensed H5N1 vaccines generate cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates of 60% to 95% against H5 clade 2.3.4.4b were observed following two doses of AS03-adjuvanted-A/Indonesia or three doses of MF59-adjuvanted-A/Vietnam vaccine. These findings suggest that the stockpiled U.S. licensed adjuvanted H5N1 vaccines generate cross-neutralizing antibodies against circulating HPAI H5N1 clade 2.3.4.4b in humans and may be useful as bridging vaccines until updated H5N1 vaccines become available.

PMID:39013430 | DOI:10.1038/s41591-024-03189-y

J Cell Biol. 2024 Sep 2;223(9):e202310030. doi: 10.1083/jcb.202310030. Epub 2024 Jul 16.

ABSTRACT

We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the four-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity and that the CCM2-TLNRD1 interaction impacts endothelial actin stress fiber and focal adhesion formation. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity.

PMID:39013281 | DOI:10.1083/jcb.202310030

Epigenetics Chromatin. 2024 Jul 16;17(1):21. doi: 10.1186/s13072-024-00545-7.

ABSTRACT

BACKGROUND: Cis-regulatory elements (CREs) play a pivotal role in gene expression regulation, allowing cells to serve diverse functions and respond to external stimuli. Understanding CREs is essential for personalized medicine and disease research, as an increasing number of genetic variants associated with phenotypes and diseases overlap with CREs. However, existing databases often focus on subsets of regulatory elements and present each identified instance of element individually, confounding the effort to obtain a comprehensive view. To address this gap, we have created CREdb, a comprehensive database with over 10 million human regulatory elements across 1,058 cell types and 315 tissues harmonized from different data sources. We curated and aligned the cell types and tissues to standard ontologies for efficient data query.

RESULTS: Data from 11 sources were curated and mapped to standard ontological terms. 11,223,434 combined elements are present in the final database, and these were merged into 5,666,240 consensus elements representing the combined ranges of the individual elements informed by their overlap. Each consensus element contains curated metadata including the number of elements supporting it and a hash linking to the source databases. The inferred activity of each consensus element in various cell-type and tissue context is also provided. Examples presented here show the potential utility of CREdb in annotating non-coding genetic variants and informing chromatin accessibility profiling analysis.

CONCLUSIONS: We developed CREdb, a comprehensive database of CREs, to simplify the analysis of CREs by providing a unified framework for researchers. CREdb compiles consensus ranges for each element by integrating the information from all instances identified across various source databases. This unified database facilitates the functional annotation of non-coding genetic variants and complements chromatin accessibility profiling analysis. CREdb will serve as an important resource in expanding our knowledge of the epigenome and its role in human diseases.

PMID:39014503 | DOI:10.1186/s13072-024-00545-7