CHROMATIN DOMAINS · Differentially Accessible Chromatin Domains and Their Transcriptional Regulatory Role in Health and Disease
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-09-01 → 2017-08-31
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
3D организацията на генома и т.нар. „хроматинови домейни“ се анализират чрез компютърни методи, за да се разбере как регулаторните региони взаимодействат с конкретни гени. Това помага за изясняване на механизмите, които управляват работата на гените при здрави хора и при заболявания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Differentially Accessible Chromatin Domains and Their Transcriptional Regulatory Role in Health and Disease
We are a computational research group, led by Dr. Tommy Kaplan, in the School of Computer Science and Engineering, the Hebrew University. Our group, established in Fall 2012, is composed of one postdoc fellow, one MD/PhD student, and six MSc students, with many active collaborations with experimental groups in Israel and abroad. We study the chromatin dynamics and the organization of the genome in 3D. For this, we are developing computational methods for integrating vast amounts of publicly available heterogeneous data and identify the organization of the genome into “Chromatin Domains” - the atomic units of genome packaging. For this, we rely on genome-wide high-throughput data. Currently, we mostly use Hi-C data from various biological conditions and tissues. Additional data we use includes DNA accessibility (DNaseI and ATAC-seq), histone modifications, including H3K27ac, H3K27me3, H3K4me1, etc. We developed computational methods that are based on Hidden Markov Models and other Dynamics Programming algorithms that integrate these genomic tracks (either in a discretize or a continuous form) and identify “natural” boundary regions and define minimal autonomous Chromatin Domains. We then re-use the Histone Modification data to identify the functional role of each. These data will be integrated with condition specific high-throughput DNA-DNA interaction data (Hi-C and ChIA-PET) to identify specific interactions between, for example, regulatory regions and their target genes.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The human genome encodes for hundreds of transcriptional programs, which facilitates the unique functions and morphologies presented by different cell types. Only recently, the role of DNA packaging into chromatin emerged as one of the major contributors to the modularity and dynamics of the genome. Here, I propose to harness my computational expertise with vast amounts of publicly available data in mice and humans, and study the internal modularity and dynamics of genome packaging, and its relation to the expression levels of underlying genes in various conditions.Specifically, the objectives of this proposal are fourfold: (1) Identify chromatin domains at a genome-wide scale. I will analyze data from hundreds of genome-wide chromatin tracks, and develop computational algorithms to segment the genome into atomic units of chromatin packaging, that open and close as homogenous blocks under various conditions and transcriptional programs. (2) Annotate and understand the functional roles of each domain. I will utilize public gene expression data and genomic maps of chromatin modifiers to annotate the role of each chromatin block, and construct an unbiased comprehensive map of the genome packaging. (3) Study the mechanisms that define, maintain and modify chromatin domains. Using sequence motifs and published binding data, I will identify chromatin regulators involved in differential domains. (4) The role of aberrant chromatin packaging in cancerous tissues. I will contrast the above domains with chromatin in cancerous tissues, and link differences to transcriptional abnormalities, thus producing a detailed set of testable hypotheses regarding the mechanisms and progression of tumors.With proven experience and proven background in genomics and computation and algorithms, I am poised to significantly contribute to our understanding of genome packaging and transcriptional regulation.
Оригинален текст от CORDIS (на английски).
Участници
- THE HEBREW UNIVERSITY OF JERUSALEM · JerusalemКоординаторИзраел
Връзки
Данни: CORDIS, © Европейски съюз