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Larsson, PontusUppsala universitet,Institutionen för cell- och molekylärbiologi
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De novo search for non-coding RNA genes in the AT-rich genome of Dictyostelium discoideum : Performance of Markov-dependent genome feature scoring
- Artikel/kapitelEngelska2008
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2008-03-17
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Cold Spring Harbor Laboratory,2008
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LIBRIS-ID:oai:DiVA.org:uu-97961
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-97961URI
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https://doi.org/10.1101/gr.069104.107DOI
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Språk:engelska
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Sammanfattning på:engelska
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Genome data are increasingly important in the computational identification of novel regulatory non-coding RNAs (ncRNAs). However, most ncRNA gene-finders are either specialized to well-characterized ncRNA gene families or require comparisons of closely related genomes. We developed a method for de novo screening for ncRNA genes with a nucleotide composition that stands out against the background genome based on a partial sum process. We compared the performance when assuming independent and first-order Markov-dependent nucleotides, respectively, and used Karlin-Altschul and Karlin-Dembo statistics to evaluate the significance of hits. We hypothesized that a first-order Markov-dependent process might have better power to detect ncRNA genes since nearest-neighbor models have been shown to be successful in predicting RNA structures. A model based on a first-order partial sum process (analyzing overlapping dinucleotides) had better sensitivity and specificity than a zeroth-order model when applied to the AT-rich genome of the amoeba Dictyostelium discoideum. In this genome, we detected 94% of previously known ncRNA genes (at this sensitivity, the false positive rate was estimated to be 25% in a simulated background). The predictions were further refined by clustering candidate genes according to sequence similarity and/or searching for an ncRNA-associated upstream element. We experimentally verified six out of 10 tested ncRNA gene predictions. We conclude that higher-order models, in combination with other information, are useful for identification of novel ncRNA gene families in single-genome analysis of D. discoideum. Our generalizable approach extends the range of genomic data that can be searched for novel ncRNA genes using well-grounded statistical methods.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hinas, AndreaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)anhin676
(författare)
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Ardell, David H.Uppsala universitet,Centrum för bioinformatik
(författare)
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Kirsebom, Leif A.Uppsala universitet,Institutionen för cell- och molekylärbiologi(Swepub:uu)leifkirs
(författare)
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Virtanen, AndersUppsala universitet,Molekylärbiologi
(författare)
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Söderbom, Fredrik
(författare)
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Uppsala universitetInstitutionen för cell- och molekylärbiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Genome Research: Cold Spring Harbor Laboratory18:6, s. 888-8991088-90511549-5469
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