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Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0.

ABSTRACT: Sequence simulation is an important tool in validating biological hypotheses as well as testing various bioinformatics and molecular evolutionary methods. Hypothesis testing relies on the representational ability of the sequence simulation method. Simple hypotheses are testable through simulation of random, homogeneously evolving sequence sets. However, testing complex hypotheses, for example, local similarities, requires simulation of sequence evolution under heterogeneous models. To this end, we previously introduced indel-Seq-Gen version 1.0 (iSGv1.0; indel, insertion/deletion). iSGv1.0 allowed heterogeneous protein evolution and motif conservation as well as insertion and deletion constraints in subsequences. Despite these advances, for complex hypothesis testing, neither iSGv1.0 nor other currently available sequence simulation methods is sufficient. indel-Seq-Gen version 2.0 (iSGv2.0) aims at simulating evolution of highly divergent DNA sequences and protein superfamilies. iSGv2.0 improves upon iSGv1.0 through the addition of lineage-specific evolution, motif conservation using PROSITE-like regular expressions, indel tracking, subsequence-length constraints, as well as coding and noncoding DNA evolution. Furthermore, we formalize the sequence representation used for iSGv2.0 and uncover a flaw in the modeling of indels used in current state of the art methods, which biases simulation results for hypotheses involving indels. We fix this flaw in iSGv2.0 by using a novel discrete stepping procedure. Finally, we present an example simulation of the calycin-superfamily sequences and compare the performance of iSGv2.0 with iSGv1.0 and random model of sequence evolution.

SUBMITTER: Strope CL

PROVIDER: S-EPMC2760465 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0.

Strope Cory L CL Abel Kevin K Scott Stephen D SD Moriyama Etsuko N EN

Molecular biology and evolution 20090803 11

Sequence simulation is an important tool in validating biological hypotheses as well as testing various bioinformatics and molecular evolutionary methods. Hypothesis testing relies on the representational ability of the sequence simulation method. Simple hypotheses are testable through simulation of random, homogeneously evolving sequence sets. However, testing complex hypotheses, for example, local similarities, requires simulation of sequence evolution under heterogeneous models. To this end, ...[more]

PMID: 19651852

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Project description:BackgroundThe Standards for Quality Improvement Reporting Excellence (SQUIRE) Guideline was published in 2008 (SQUIRE 1.0) and was the first publication guideline specifically designed to advance the science of healthcare improvement. Advances in the discipline of improvement prompted us to revise it. We adopted a novel approach to the revision by asking end-users to 'road test' a draft version of SQUIRE 2.0. The aim was to determine whether they understood and implemented the guidelines as intended by the developers.MethodsForty-four participants were assigned a manuscript section (ie, introduction, methods, results, discussion) and asked to use the draft Guidelines to guide their writing process. They indicated the text that corresponded to each SQUIRE item used and submitted it along with a confidential survey. The survey examined usability of the Guidelines using Likert-scaled questions and participants' interpretation of key concepts in SQUIRE using open-ended questions. On the submitted text, we evaluated concordance between participants' item usage/interpretation and the developers' intended application. For the survey, the Likert-scaled responses were summarised using descriptive statistics and the open-ended questions were analysed by content analysis.ResultsConsistent with the SQUIRE Guidelines' recommendation that not every item be included, less than one-third (n=14) of participants applied every item in their section in full. Of the 85 instances when an item was partially used or was omitted, only 7 (8.2%) of these instances were due to participants not understanding the item. Usage of Guideline items was highest for items most similar to standard scientific reporting (ie, 'Specific aim of the improvement' (introduction), 'Description of the improvement' (methods) and 'Implications for further studies' (discussion)) and lowest (<20% of the time) for those unique to healthcare improvement (ie, 'Assessment methods for context factors that contributed to success or failure' and 'Costs and strategic trade-offs'). Items unique to healthcare improvement, specifically 'Evolution of the improvement', 'Context elements that influenced the improvement', 'The logic on which the improvement was based', 'Process and outcome measures', demonstrated poor concordance between participants' interpretation and developers' intended application.ConclusionsUser testing of a draft version of SQUIRE 2.0 revealed which items have poor concordance between developer intent and author usage, which will inform final editing of the Guideline and development of supporting supplementary materials. It also identified the items that require special attention when teaching about scholarly writing in healthcare improvement.

Dataset Information

Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0.

Publications

Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0.

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