Browsing by Subject "gene ontology"

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Open Access
Div-blast: Diversification of sequence search results
(Public Library of Science, 2014) Eser, E.; Can, T.; Ferhatosmanoglu H.
Sequence similarity tools, such as BLAST, seek sequences most similar to a query from a database of sequences. They return results significantly similar to the query sequence and that are typically highly similar to each other. Most sequence analysis tasks in bioinformatics require an exploratory approach, where the initial results guide the user to new searches. However, diversity has not yet been considered an integral component of sequence search tools for this discipline. Some redundancy can be avoided by introducing non-redundancy during database construction, but it is not feasible to dynamically set a level of non-redundancy tailored to a query sequence. We introduce the problem of diverse search and browsing in sequence databases that produce non-redundant results optimized for any given query. We define diversity measures for sequences and propose methods to obtain diverse results extracted from current sequence similarity search tools. We also propose a new measure to evaluate the diversity of a set of sequences that is returned as a result of a sequence similarity query. We evaluate the effectiveness of the proposed methods in post-processing BLAST and PSIBLAST results. We also assess the functional diversity of the returned results based on available Gene Ontology annotations. Additionally, we include a comparison with a current redundancy elimination tool, CD-HIT. Our experiments show that the proposed methods are able to achieve more diverse yet significant result sets compared to static non-redundancy approaches. In both sequencebased and functional diversity evaluation, the proposed diversification methods significantly outperform original BLAST results and other baselines. A web based tool implementing the proposed methods, Div-BLAST, can be accessed at cedar.cs.bilkent.edu.tr/Div-BLAST © 2014 Eser et al.
Open Access
PATZ1 is a DNA damage-responsive transcription factor that inhibits p53 function
(American Society for Microbiology, 2015) Keskin, N.; Deniz, E.; Eryilmaz J.; Un, M.; Batur, T.; Ersahin, T.; Atalay, R.C.; Sakaguchi, S.; Ellmeier W.; Erman, B.
Insults to cellular health cause p53 protein accumulation, and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel role of PATZ1 as an inhibitor of the p53 protein marks its gene as a proto-oncogene. PATZ1-deficient cells have reduced proliferative capacity, which we assessed by transcriptome sequencing (RNA-Seq) and real-time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage-inducing drug doxorubicin results in the loss of the PATZ1 transcription factor as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53-dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. © 2015, American Society for Microbiology.