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  1. Article ; Online: GRaNIE and GRaNPA

    Aryan Kamal / Christian Arnold / Annique Claringbould / Rim Moussa / Nila H Servaas / Maksim Kholmatov / Neha Daga / Daria Nogina / Sophia Mueller‐Dott / Armando Reyes‐Palomares / Giovanni Palla / Olga Sigalova / Daria Bunina / Caroline Pabst / Judith B Zaugg

    Molecular Systems Biology, Vol 19, Iss 6, Pp n/a-n/a (2023)

    inference and evaluation of enhancer‐mediated gene regulatory networks

    2023  

    Abstract: Abstract Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell‐type‐specific process regulated by transcription factors (TFs), ... ...

    Abstract Abstract Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell‐type‐specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell‐type‐specific gene regulatory networks (GRN). Equally important, we lack an unbiased way of assessing the biological significance of inferred GRNs since no complete ground truth exists. To address these gaps, we present GRaNIE (Gene Regulatory Network Inference including Enhancers) and GRaNPA (Gene Regulatory Network Performance Analysis). GRaNIE (https://git.embl.de/grp‐zaugg/GRaNIE) builds enhancer‐mediated GRNs based on covariation of chromatin accessibility and RNA‐seq across samples (e.g. individuals), while GRaNPA (https://git.embl.de/grp‐zaugg/GRaNPA) assesses the performance of GRNs for predicting cell‐type‐specific differential expression. We demonstrate their power by investigating gene regulatory mechanisms underlying the response of macrophages to infection, cancer and common genetic traits including autoimmune diseases. Finally, our methods identify the TF PURA as a putative regulator of pro‐inflammatory macrophage polarisation.
    Keywords enhancers ; gene regulatory networks ; macrophage biology ; multiomics data integration ; transcriptional regulation ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex.

    Tamara Salloum / Rim Moussa / Ryan Rahy / Jospin Al Deek / Ibrahim Khalifeh / Rana El Hajj / Neil Hall / Robert P Hirt / Sima Tokajian

    PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e

    2020  Volume 0008684

    Abstract: Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding ... ...

    Abstract Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Subject code 572
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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