Abstract:
:Computational and mathematical modelling has become a valuable tool for investigating biological systems. Modelling enables prediction of how biological components interact to deliver system-level properties and extrapolation of biological system performance to contexts and experimental conditions where this is unknown. A model's value hinges on knowing that it faithfully represents the biology under the contexts of use, or clearly ascertaining otherwise and thus motivating further model refinement. These qualities are evaluated through calibration, typically formulated as identifying model parameter values that align model and biological behaviours as measured through a metric applied to both. Calibration is critical to modelling but is often underappreciated. A failure to appropriately calibrate risks unrepresentative models that generate erroneous insights. Here, we review a suite of strategies to more rigorously challenge a model's representation of a biological system. All are motivated by features of biological systems, and illustrative examples are drawn from the modelling literature. We examine the calibration of a model against distributions of biological behaviours or outcomes, not only average values. We argue for calibration even where model parameter values are experimentally ascertained. We explore how single metrics can be non-distinguishing for complex systems, with multiple-component dynamic and interaction configurations giving rise to the same metric output. Under these conditions, calibration is insufficiently constraining and the model non-identifiable: multiple solutions to the calibration problem exist. We draw an analogy to curve fitting and argue that calibrating a biological model against a single experiment or context is akin to curve fitting against a single data point. Though useful for communicating model results, we explore how metrics that quantify heavily emergent properties may not be suitable for use in calibration. Lastly, we consider the role of sensitivity and uncertainty analysis in calibration and the interpretation of model results. Our goal in this manuscript is to encourage a deeper consideration of calibration, and how to increase its capacity to either deliver faithful models or demonstrate them otherwise.
journal_name
Brief Bioinformjournal_title
Briefings in bioinformaticsauthors
Read MN,Alden K,Timmis J,Andrews PSdoi
10.1093/bib/bby092subject
Has Abstractpub_date
2018-09-18 00:00:00eissn
1467-5463issn
1477-4054pii
5099477pub_type
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
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journal_title:Briefings in bioinformatics
pub_type: 历史文章,杂志文章
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
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journal_title:Briefings in bioinformatics
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doi:10.1093/bib/3.1.18
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pub_type: 杂志文章,评审
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbt011
更新日期:2014-07-01 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbp056
更新日期:2010-05-01 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa310
更新日期:2020-12-15 00:00:00
abstract::Small noncoding RNAs (sRNA/sncRNAs) are generated from different genomic loci and play important roles in biological processes, such as cell proliferation and the regulation of gene expression. Next-generation sequencing (NGS) has provided an unprecedented opportunity to discover and quantify diverse kinds of sncRNA, ...
journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbz151
更新日期:2021-01-18 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa197
更新日期:2020-09-08 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa187
更新日期:2020-09-02 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbx128
更新日期:2019-01-18 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 历史文章,杂志文章,评审
doi:10.1093/bib/bby063
更新日期:2019-11-27 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/1.2.190
更新日期:2000-05-01 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbz054
更新日期:2020-07-15 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbx014
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1093/bib/bby124
更新日期:2020-03-23 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa369
更新日期:2021-01-06 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa213
更新日期:2020-09-21 00:00:00
abstract::SARS-CoV-2 is an intensively investigated virus from the order Nidovirales (Coronaviridae family) that causes COVID-19 disease in humans. Through enormous scientific effort, thousands of viral strains have been sequenced to date, thereby creating a strong background for deep bioinformatics studies of the SARS-CoV-2 ge...
journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbaa385
更新日期:2020-12-21 00:00:00
abstract::Phenotypes have gained increased notoriety in the clinical and biological domain owing to their application in numerous areas such as the discovery of disease genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined as observable characteristics of organisms, can be seen as one of the bridges th...
journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbv083
更新日期:2016-09-01 00:00:00
abstract::Transposable elements (TEs) are an important source of human genetic variation with demonstrable effects on phenotype. Recently, a number of computational methods for the detection of polymorphic TE (polyTE) insertion sites from next-generation sequence data have been developed. The use of such tools will become incre...
journal_title:Briefings in bioinformatics
pub_type: 杂志文章
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更新日期:2017-11-01 00:00:00
abstract::Gene set analysis (GSA) is one of the methods of choice for analyzing the results of current omics studies; however, it has been mainly developed to analyze mRNA (microarray, RNA-Seq) data. The following review includes an update regarding general methods and resources for GSA and then emphasizes GSA methods and tools...
journal_title:Briefings in bioinformatics
pub_type: 杂志文章
doi:10.1093/bib/bbz090
更新日期:2020-09-25 00:00:00
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journal_title:Briefings in bioinformatics
pub_type: 杂志文章,评审
doi:10.1093/bib/bby038
更新日期:2019-09-27 00:00:00