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Sökning: WFRF:(Sweedler Jonathan) > (2010-2014)

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1.
  • Akhtar, Malik N., et al. (författare)
  • Accurate Assignment of Significance to Neuropeptide Identifications Using Monte Carlo K-Permuted Decoy Databases
  • 2014
  • Ingår i: PLOS ONE. - 1932-6203. ; 9:10, s. e111112-
  • Tidskriftsartikel (refereegranskat)abstract
    • In support of accurate neuropeptide identification in mass spectrometry experiments, novel Monte Carlo permutation testing was used to compute significance values. Testing was based on k-permuted decoy databases, where k denotes the number of permutations. These databases were integrated with a range of peptide identification indicators from three popular open-source database search software (OMSSA, Crux, and X! Tandem) to assess the statistical significance of neuropeptide spectra matches. Significance p-values were computed as the fraction of the sequences in the database with match indicator value better than or equal to the true target spectra. When applied to a test-bed of all known manually annotated mouse neuropeptides, permutation tests with k-permuted decoy databases identified up to 100% of the neuropeptides at p-value < 10(-5). The permutation test p-values using hyperscore (X! Tandem), E-value (OMSSA) and Sp score (Crux) match indicators outperformed all other match indicators. The robust performance to detect peptides of the intuitive indicator "number of matched ions between the experimental and theoretical spectra" highlights the importance of considering this indicator when the p-value was borderline significant. Our findings suggest permutation decoy databases of size 1x10(5) are adequate to accurately detect neuropeptides and this can be exploited to increase the speed of the search. The straightforward Monte Carlo permutation testing (comparable to a zero order Markov model) can be easily combined with existing peptide identification software to enable accurate and effective neuropeptide detection. The source code is available at http://stagbeetle.animal.uiuc.edu/pepshop/MSMSpermutationtesting.
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2.
  • Akhtar, Malik N., et al. (författare)
  • Evaluation of Database Search Programs for Accurate Detection of Neuropeptides in Tandem Mass Spectrometry Experiments
  • 2012
  • Ingår i: Journal of Proteome Research. - 1535-3893 .- 1535-3907. ; 11:12, s. 6044-6055
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropeptide identification in mass spectrometry experiments using database search programs developed for proteins is challenging. Unlike proteins, the detection of the complete sequence using a single spectrum is required to identify neuropeptides or prohormone peptides. This study compared the performance of three open-source programs used to identify proteins, OMSSA, X!Tandem and Crux, to identify prohormone peptides. From a target database of 7850 prohormone peptides, 23550 query spectra were simulated across different scenarios. Crux was the only program that correctly matched all peptides regardless of p-value and at p-value < 1 X 10(-2), 33%, 64%, and >75%, of the 5, 6, and >= 7 amino acid-peptides were detected. Crux also had the best performance in the identification of peptides from chimera spectra and in a variety of missing ion scenarios. OMSSA, X!Tandem and Crux correctly detected 98.9% (99.9%), 93.9% (97.4%) and 88.7% (98.3%) of the peptides at E- or p-value < 1 X 10(-6) (< 1 X 10(-2)), respectively. OMSSA and X! Tandem outperformed the other programs in significance level and computational speed, respectively. A consensus approach is not recommended because some prohormone peptides were only identified by one program.
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3.
  • Akhtar, Malik N., et al. (författare)
  • Identification of best indicators of peptide-spectrum match using a permutation resampling approach
  • 2014
  • Ingår i: Journal of Bioinformatics and Computational Biology. - 0219-7200 .- 1757-6334. ; 12:5, s. 1440001-
  • Tidskriftsartikel (refereegranskat)abstract
    • Various indicators of observed-theoretical spectrum matches were compared and the resulting statistical significance was characterized using permutation resampling. Novel decoy databases built by resampling the terminal positions of peptide sequences were evaluated to identify the conditions for accurate computation of peptide match significance levels. The methodology was tested on real and manually curated tandem mass spectra from peptides across a wide range of sizes. Spectra match indicators from complementary database search programs were pro filed and optimal indicators were identified. The combination of the optimal indicator and permuted decoy databases improved the calculation of the peptide match significance compared to the approaches currently implemented in the database search programs that rely on distributional assumptions. Permutation tests using p-values obtained from software-dependent matching scores and E-values outperformed permutation tests using all other indicators. The higher overlap in matches between the database search programs when using end permutation compared to existing approaches con firmed the superiority of the end permutation method to identify peptides. The combination of effective match indicators and the end permutation method is recommended for accurate detection of peptides.
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4.
  • Warren, Wesley C, et al. (författare)
  • The genome of a songbird
  • 2010
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 464:7289, s. 757-762
  • Tidskriftsartikel (refereegranskat)abstract
    • The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.
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