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New algorithm and ChIP-analysis identifies candidate functional SNPs
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Centrum för bioinformatik.
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Ingår i: PNASArtikel i tidskrift (Refereegranskat) Submitted
Identifikatorer
URN: urn:nbn:se:uu:diva-97707OAI: oai:DiVA.org:uu-97707DiVA, id: diva2:172748
Tillgänglig från: 2008-11-06 Skapad: 2008-11-06Bibliografiskt granskad
Ingår i avhandling
1. A Bioinformatics Study of Human Transcriptional Regulation
Öppna denna publikation i ny flik eller fönster >>A Bioinformatics Study of Human Transcriptional Regulation
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Regulation of transcription is a central mechanism in all living cells that now can be investigated with high-throughput technologies. Data produced from such experiments give new insights to how transcription factors (TFs) coordinate the gene transcription and thereby regulate the amounts of proteins produced. These studies are also important from a medical perspective since TF proteins are often involved in disease. To learn more about transcriptional regulation, we have developed strategies for analysis of data from microarray and massively parallel sequencing (MPS) experiments.

Our computational results consist of methods to handle the steadily increasing amount of data from high-throughput technologies. Microarray data analysis tools have been assembled in the LCB-Data Warehouse (LCB-DWH) (paper I), and other analysis strategies have been developed for MPS data (paper V). We have also developed a de novo motif search algorithm called BCRANK (paper IV).

The analysis has lead to interesting biological findings in human liver cells (papers II-V). The investigated TFs appeared to bind at several thousand sites in the genome, that we have identified at base pair resolution. The investigated histone modifications are mainly found downstream of transcription start sites, and correlated to transcriptional activity. These histone marks are frequently found for pairs of genes in a bidirectional conformation. Our results suggest that a TF can bind in the shared promoter of two genes and regulate both of them.

From a medical perspective, the genes bound by the investigated TFs are candidates to be involved in metabolic disorders. Moreover, we have developed a new strategy to detect single nucleotide polymorphisms (SNPs) that disrupt the binding of a TF (paper IV). We further demonstrated that SNPs can affect transcription in the immediate vicinity. Ultimately, our method may prove helpful to find disease-causing regulatory SNPs.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2008. s. 52
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 566
Nyckelord
bioinformatics, microarray, ChIP-chip, ChIP-seq, transcription factor, histone modification, motif search
Nationell ämneskategori
Bioinformatik (beräkningsbiologi)
Identifikatorer
urn:nbn:se:uu:diva-9346 (URN)978-91-554-7324-2 (ISBN)
Disputation
2008-11-28, C8:305, BMC, Husargatan 3, Uppsala, 09:00
Opponent
Handledare
Tillgänglig från: 2008-11-06 Skapad: 2008-11-06 Senast uppdaterad: 2018-01-13Bibliografiskt granskad

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