Research Grants 19/07382-2 - Genômica, Epigenômica - BV FAPESP
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Multi-omics integration for detection of novel chromatin biomarkers in human disorders: towards a better understanding of disease mechanisms and novel therapies

Abstract

Next-generation sequencing and omics technologies are continuously increasing our capacity to measure multiple layers of information in complex human diseases. In recent years, the assay for transposase-accessible chromatin followed by sequencing (ATAC-seq) enabled to interrogate the functional open chromatin (regulomes) of primary cells, rare cell populations and single cells, charting the previously unknown atlas of enhancers and cis-regulatory elements in human diseases. In parallel, advances in transcriptomics have enabled the measurement of gene and isoform expression in both bulk and single cells. In this project, we propose the development of state-of-the-art machine learning and deep learning approaches for large scale integrative analysis of regulomes and transcriptomes, aiming at finding open-chromatin regions driving disease. These approaches will be able to model heterogeneity in large patient cohorts as well as to discover chromatin enhancers impacting transcription of key disease-associated genes. We expect to find a novel type of chromatin-based biomarkers with potential prognostic and diagnostic value in several diseases, including solid tumors, blood cancers, neurological and autoimmune disorders. We also propose the application of ATAC-seq in clinical settings for patient monitoring through the development and validation of a chromatin-based fingerprinting of blood and tissues, that could replace conventional cytometry for profiling cellular composition of disease samples. In addition, the identification of new elements likely to regulate gene expression in normal and disease states is critical not only to better understand the mechanisms underlying disease but also to identify potential new targets for treatment. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GALVAO, ISABELLA C.; KANDRATAVICIUS, LUDMYLA; MESSIAS, LAUANA A.; ATHIE, MARIA C. P.; ASSIS-MENDONCA, GUILHERME R.; ALVIM, MARINA K. M.; GHIZONI, ENRICO; TEDESCHI, HELDER; YASUDA, CLARISSA L.; CENDES, FERNANDO; et al. Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures. SCIENTIFIC REPORTS, v. 13, n. 1, p. 10-pg., . (13/07559-3, 20/04780-4, 19/08259-0, 20/15112-2, 22/01530-2, 19/07382-2)
GALVAO, ISABELLA C.; LEMOINE, MANUELA; MESSIAS, LAUANA A.; ARAUJO, PATRICIA A. O. R. A.; GERALDIS, JAQUELINE C.; YASUDA, CLARISSA L.; ALVIM, MARINA K. M.; GHIZONI, ENRICO; TEDESCHI, HELDER; CENDES, FERNANDO; et al. Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia. ISCIENCE, v. 27, n. 12, p. 20-pg., . (20/06168-4, 19/07382-2, 13/07559-3, 22/01530-2)

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