1,749,182 research outputs found
Accounting for immunoprecipitation efficiencies in the statistical analysis of ChIP-seq data
Background: ImmunoPrecipitation (IP) efficiencies may vary largely between different antibodies and between repeated experiments with the same antibody. These differences have a large impact on the quality of ChIP-seq data: a more efficient experiment will necessarily lead to a higher signal to background ratio, and therefore to an apparent larger number of enriched regions, compared to a less efficient experiment. In this paper, we show how IP efficiencies can be explicitly accounted for in the joint statistical modelling of ChIP-seq data.
Results: We fit a latent mixture model to eight experiments on two proteins, from two laboratories where different antibodies are used for the two proteins. We use the model parameters to estimate the efficiencies of individual experiments, and find that these are clearly different for the different laboratories, and amongst technical replicates from the same lab. When we account for ChIP efficiency, we find more regions bound in the more efficient experiments than in the less efficient ones, at the same false discovery rate. A priori knowledge of the same number of binding sites across experiments can also be included in the model for a more robust detection of differentially bound regions among two different proteins.
Conclusions: We propose a statistical model for the detection of enriched and differentially bound regions from multiple ChIP-seq data sets. The framework that we present accounts explicitly for IP efficiencies in ChIP-seq data, and allows to model jointly, rather than individually, replicates and experiments from different proteins, leading to more robust biological conclusions.
Fine-tuning structural RNA alignments in the twilight zone
Bremges A, Schirmer S, Giegerich R. Fine-tuning structural RNA alignments in the twilight zone. BMC Bioinformatics. 2010;11(1): 222.Background A widely used method to find conserved secondary structure in RNA is to first construct a multiple sequence alignment, and then fold the alignment, optimizing a score based on thermodynamics and covariance. This method works best around 75% sequence similarity. However, in a "twilight zone" below 55% similarity, the sequence alignment tends to obscure the covariance signal used in the second phase. Therefore, while the overall shape of the consensus structure may still be found, the degree of conservation cannot be estimated reliably. Results Based on a combination of available methods, we present a method named planACstar for improving structure conservation in structural alignments in the twilight zone. After constructing a consensus structure by alignment folding, planACstar abandons the original sequence alignment, refolds the sequences individually, but consistent with the consensus, aligns the structures, irrespective of sequence, by a pure structure alignment method, and derives an improved sequence alignment from the alignment of structures, to be re-submitted to alignment folding, etc.. This circle may be iterated as long as structural conservation improves, but normally, one step suffices. Conclusions Employing the tools ClustalW, RNAalifold, and RNAforester, we find that for sequences with 30-55% sequence identity, structural conservation can be improved by 10% on average, with a large variation, measured in terms of RNAalifold's own criterion, the structure conservation index
A text-mining system for extracting metabolic reactions from full-text articles
Background: Increasingly biological text mining research is focusing on the extraction of complex relationships
relevant to the construction and curation of biological networks and pathways. However, one important category of
pathway—metabolic pathways—has been largely neglected.
Here we present a relatively simple method for extracting metabolic reaction information from free text that scores
different permutations of assigned entities (enzymes and metabolites) within a given sentence based on the presence
and location of stemmed keywords. This method extends an approach that has proved effective in the context of the
extraction of protein–protein interactions.
Results: When evaluated on a set of manually-curated metabolic pathways using standard performance criteria, our
method performs surprisingly well. Precision and recall rates are comparable to those previously achieved for the
well-known protein-protein interaction extraction task.
Conclusions: We conclude that automated metabolic pathway construction is more tractable than has often been
assumed, and that (as in the case of protein–protein interaction extraction) relatively simple text-mining approaches can prove surprisingly effective. It is hoped that these results will provide an impetus to further research and act as a useful benchmark for judging the performance of more sophisticated methods that are yet to be developed
Whelan, J T, 2105
This record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/425176Surname: WHELAN. Given Name(s) or Initials: J T. Military Service Number or Last Known Location: 2105. Missing, Wounded and Prisoner of War Enquiry Card Index Number: 29081.251035
Item: [2016.0049.57437] "Whelan, J T, 2105
Santa Fe (ATSF) 2105
A photograph postcard showing Santa Fe 2105, 0-6-0 (BLW), class 2100, San Francisco, CA
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