Strategies for calibrating models of biology.

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 Bioinform

authors

Read MN,Alden K,Timmis J,Andrews PS

doi

10.1093/bib/bby092

subject

Has Abstract

pub_date

2018-09-18 00:00:00

eissn

1467-5463

issn

1477-4054

pii

5099477

pub_type

杂志文章
  • Systematic review of computational methods for identifying miRNA-mediated RNA-RNA crosstalk.

    abstract::Posttranscriptional crosstalk and communication between RNAs yield large regulatory competing endogenous RNA (ceRNA) networks via shared microRNAs (miRNAs), as well as miRNA synergistic networks. The ceRNA crosstalk represents a novel layer of gene regulation that controls both physiological and pathological processes...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx137

    authors: Li Y,Jin X,Wang Z,Li L,Chen H,Lin X,Yi S,Zhang Y,Xu J

    更新日期:2019-07-19 00:00:00

  • Bioinformatics education--perspectives and challenges out of Africa.

    abstract::The discipline of bioinformatics has developed rapidly since the complete sequencing of the first genomes in the 1990s. The development of many high-throughput techniques during the last decades has ensured that bioinformatics has grown into a discipline that overlaps with, and is required for, the modern practice of ...

    journal_title:Briefings in bioinformatics

    pub_type: 历史文章,杂志文章

    doi:10.1093/bib/bbu022

    authors: Tastan Bishop Ö,Adebiyi EF,Alzohairy AM,Everett D,Ghedira K,Ghouila A,Kumuthini J,Mulder NJ,Panji S,Patterton HG,H3ABioNet Consortium.,H3Africa Consortium.

    更新日期:2015-03-01 00:00:00

  • Tools for the functional interpretation of metabolomic experiments.

    abstract::The so-called 'omics' approaches used in modern biology aim at massively characterizing the molecular repertories of living systems at different levels. Metabolomics is one of the last additions to the 'omics' family and it deals with the characterization of the set of metabolites in a given biological system. As meta...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbs055

    authors: Chagoyen M,Pazos F

    更新日期:2013-11-01 00:00:00

  • Using prior knowledge from cellular pathways and molecular networks for diagnostic specimen classification.

    abstract::For many complex diseases, an earlier and more reliable diagnosis is considered a key prerequisite for developing more effective therapies to prevent or delay disease progression. Classical statistical learning approaches for specimen classification using omics data, however, often cannot provide diagnostic models wit...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbv044

    authors: Glaab E

    更新日期:2016-05-01 00:00:00

  • Pioneering topological methods for network-based drug-target prediction by exploiting a brain-network self-organization theory.

    abstract::The bipartite network representation of the drug-target interactions (DTIs) in a biosystem enhances understanding of the drugs' multifaceted action modes, suggests therapeutic switching for approved drugs and unveils possible side effects. As experimental testing of DTIs is costly and time-consuming, computational pre...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx041

    authors: Durán C,Daminelli S,Thomas JM,Haupt VJ,Schroeder M,Cannistraci CV

    更新日期:2018-11-27 00:00:00

  • The computational challenges of applying comparative-based computational methods to whole genomes.

    abstract::The explosion in genomic sequence available in public databases has resulted in an unprecedented opportunity for computational whole genome analyses. A number of promising comparative-based approaches have been developed for gene finding, regulatory element discovery and other purposes, and it is clear that these tool...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/3.1.18

    authors: Dubchak I,Pachter L

    更新日期:2002-03-01 00:00:00

  • Understanding the unimodal distributions of cancer occurrence rates: it takes two factors for a cancer to occur.

    abstract::Data from the SEER reports reveal that the occurrence rate of a cancer type generally follows a unimodal distribution over age, peaking at an age that is cancer-type specific and ranges from 30+ through 70+. Previous studies attribute such bell-shaped distributions to the reduced proliferative potential in senior year...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa349

    authors: Qiu S,An Z,Tan R,He PA,Jing J,Li H,Wu S,Xu Y

    更新日期:2020-12-30 00:00:00

  • Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

    abstract::Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing wide...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx091

    authors: Yang Q,Wang S,Dai E,Zhou S,Liu D,Liu H,Meng Q,Jiang B,Jiang W

    更新日期:2019-01-18 00:00:00

  • Automated glycopeptide analysis--review of current state and future directions.

    abstract::Glycosylation of proteins is involved in immune defense, cell-cell adhesion, cellular recognition and pathogen binding and is one of the most common and complex post-translational modifications. Science is still struggling to assign detailed mechanisms and functions to this form of conjugation. Even the structural ana...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbs045

    authors: Dallas DC,Martin WF,Hua S,German JB

    更新日期:2013-05-01 00:00:00

  • GenoPheno: cataloging large-scale phenotypic and next-generation sequencing data within human datasets.

    abstract::Precision medicine promises to revolutionize treatment, shifting therapeutic approaches from the classical one-size-fits-all to those more tailored to the patient's individual genomic profile, lifestyle and environmental exposures. Yet, to advance precision medicine's main objective-ensuring the optimum diagnosis, tre...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa033

    authors: Gutiérrez-Sacristán A,De Niz C,Kothari C,Kong SW,Mandl KD,Avillach P

    更新日期:2021-01-18 00:00:00

  • Reproducible probe-level analysis of the Affymetrix Exon 1.0 ST array with R/Bioconductor.

    abstract::The presence of different transcripts of a gene across samples can be analysed by whole-transcriptome microarrays. Reproducing results from published microarray data represents a challenge owing to the vast amounts of data and the large variety of preprocessing and filtering steps used before the actual analysis is ca...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbt011

    authors: Rodrigo-Domingo M,Waagepetersen R,Bødker JS,Falgreen S,Kjeldsen MK,Johnsen HE,Dybkær K,Bøgsted M

    更新日期:2014-07-01 00:00:00

  • BioModels.net Web Services, a free and integrated toolkit for computational modelling software.

    abstract::Exchanging and sharing scientific results are essential for researchers in the field of computational modelling. BioModels.net defines agreed-upon standards for model curation. A fundamental one, MIRIAM (Minimum Information Requested in the Annotation of Models), standardises the annotation and curation process of qua...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbp056

    authors: Li C,Courtot M,Le Novère N,Laibe C

    更新日期:2010-05-01 00:00:00

  • Deep learning for brain disorders: from data processing to disease treatment.

    abstract::In order to reach precision medicine and improve patients' quality of life, machine learning is increasingly used in medicine. Brain disorders are often complex and heterogeneous, and several modalities such as demographic, clinical, imaging, genetics and environmental data have been studied to improve their understan...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa310

    authors: Burgos N,Bottani S,Faouzi J,Thibeau-Sutre E,Colliot O

    更新日期:2020-12-15 00:00:00

  • Small noncoding RNA discovery and profiling with sRNAtools based on high-throughput sequencing.

    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

    authors: Liu Q,Ding C,Lang X,Guo G,Chen J,Su X

    更新日期:2021-01-18 00:00:00

  • Extended application of genomic selection to screen multiomics data for prognostic signatures of prostate cancer.

    abstract::Prognostic tests using expression profiles of several dozen genes help provide treatment choices for prostate cancer (PCa). However, these tests require improvement to meet the clinical need for resolving overtreatment, which continues to be a pervasive problem in PCa management. Genomic selection (GS) methodology, wh...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa197

    authors: Li R,Wang S,Cui Y,Qu H,Chater JM,Zhang L,Wei J,Wang M,Xu Y,Yu L,Lu J,Feng Y,Zhou R,Huang Y,Ma R,Zhu J,Zhong W,Jia Z

    更新日期:2020-09-08 00:00:00

  • Proteome-scale analysis of phase-separated proteins in immunofluorescence images.

    abstract::Phase separation is an important mechanism that mediates the spatial distribution of proteins in different cellular compartments. While phase-separated proteins share certain sequence characteristics, including intrinsically disordered regions (IDRs) and prion-like domains, such characteristics are insufficient for ma...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa187

    authors: Yu C,Shen B,You K,Huang Q,Shi M,Wu C,Chen Y,Zhang C,Li T

    更新日期:2020-09-02 00:00:00

  • Advanced bioinformatics methods for practical applications in proteomics.

    abstract::Mass spectrometry (MS)-based proteomics has undergone rapid advancements in recent years, creating challenging problems for bioinformatics. We focus on four aspects where bioinformatics plays a crucial role (and proteomics is needed for clinical application): peptide-spectra matching (PSM) based on the new data-indepe...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx128

    authors: Goh WWB,Wong L

    更新日期:2019-01-18 00:00:00

  • A brief history of bioinformatics.

    abstract::It is easy for today's students and researchers to believe that modern bioinformatics emerged recently to assist next-generation sequencing data analysis. However, the very beginnings of bioinformatics occurred more than 50 years ago, when desktop computers were still a hypothesis and DNA could not yet be sequenced. T...

    journal_title:Briefings in bioinformatics

    pub_type: 历史文章,杂志文章,评审

    doi:10.1093/bib/bby063

    authors: Gauthier J,Vincent AT,Charette SJ,Derome N

    更新日期:2019-11-27 00:00:00

  • Data warehousing in molecular biology.

    abstract::In the business and healthcare sectors data warehousing has provided effective solutions for information usage and knowledge discovery from databases. However, data warehousing applications in the biological research and development (R&D) sector are lagging far behind. The fuzziness and complexity of biological data r...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/1.2.190

    authors: Schönbach C,Kowalski-Saunders P,Brusic V

    更新日期:2000-05-01 00:00:00

  • RNA-mediated translation regulation in viral genomes: computational advances in the recognition of sequences and structures.

    abstract::RNA structures are widely distributed across all life forms. The global conformation of these structures is defined by a variety of constituent structural units such as helices, hairpin loops, kissing-loop motifs and pseudoknots, which often behave in a modular way. Their ubiquitous distribution is associated with a v...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbz054

    authors: Gupta A,Bansal M

    更新日期:2020-07-15 00:00:00

  • Circular RNA identification based on multiple seed matching.

    abstract::Computational detection methods have been widely used in studies on the biogenesis and the function of circular RNAs (circRNAs). However, all of the existing tools showed disadvantages on certain aspects of circRNA detection. Here, we propose an improved multithreading detection tool, CIRI2, which used an adapted maxi...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbx014

    authors: Gao Y,Zhang J,Zhao F

    更新日期:2018-09-28 00:00:00

  • Exploring the function of genetic variants in the non-coding genomic regions: approaches for identifying human regulatory variants affecting gene expression.

    abstract::Understanding the genetic basis of human traits/diseases and the underlying mechanisms of how these traits/diseases are affected by genetic variations is critical for public health. Current genome-wide functional genomics data uncovered a large number of functional elements in the noncoding regions of human genome, pr...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bbu018

    authors: Li MJ,Yan B,Sham PC,Wang J

    更新日期:2015-05-01 00:00:00

  • Empirical comparison and analysis of web-based cell-penetrating peptide prediction tools.

    abstract::Cell-penetrating peptides (CPPs) facilitate the delivery of therapeutically relevant molecules, including DNA, proteins and oligonucleotides, into cells both in vitro and in vivo. This unique ability explores the possibility of CPPs as therapeutic delivery and its potential applications in clinical therapy. Over the l...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bby124

    authors: Su R,Hu J,Zou Q,Manavalan B,Wei L

    更新日期:2020-03-23 00:00:00

  • Towards deep phenotyping pregnancy: a systematic review on artificial intelligence and machine learning methods to improve pregnancy outcomes.

    abstract:OBJECTIVE:Development of novel informatics methods focused on improving pregnancy outcomes remains an active area of research. The purpose of this study is to systematically review the ways that artificial intelligence (AI) and machine learning (ML), including deep learning (DL), methodologies can inform patient care d...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa369

    authors: Davidson L,Boland MR

    更新日期:2021-01-06 00:00:00

  • AlzRiskMR database: an online database for the impact of exposure factors on Alzheimer's disease.

    abstract::In view of great difficulties in the pathogenesis analysis of Alzheimer's disease (AD) presently, profiling the modifiable risk factors is crucial for early detection and intervention of AD. However, the causal associations among them have yet to be identified, and the effective integration and application of these da...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章

    doi:10.1093/bib/bbaa213

    authors: Wang Z,Meng L,Liu H,Shen L,Ji HF

    更新日期:2020-09-21 00:00:00

  • SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci.

    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

    authors: Goswami P,Bartas M,Lexa M,Bohálová N,Volná A,Červeň J,Červeňová V,Pečinka P,Špunda V,Fojta M,Brázda V

    更新日期:2020-12-21 00:00:00

  • The digital revolution in phenotyping.

    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

    authors: Oellrich A,Collier N,Groza T,Rebholz-Schuhmann D,Shah N,Bodenreider O,Boland MR,Georgiev I,Liu H,Livingston K,Luna A,Mallon AM,Manda P,Robinson PN,Rustici G,Simon M,Wang L,Winnenburg R,Dumontier M

    更新日期:2016-09-01 00:00:00

  • Benchmarking computational tools for polymorphic transposable element detection.

    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

    doi:10.1093/bib/bbw072

    authors: Rishishwar L,Mariño-Ramírez L,Jordan IK

    更新日期:2017-11-01 00:00:00

  • Gene set analysis methods for the functional interpretation of non-mRNA data-Genomic range and ncRNA data.

    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

    authors: Mora A

    更新日期:2020-09-25 00:00:00

  • Survey of miRNA-miRNA cooperative regulation principles across cancer types.

    abstract::Cooperative regulation among multiple microRNAs (miRNAs) is a complex type of posttranscriptional regulation in human; however, the global view of the system-level regulatory principles across cancers is still unclear. Here, we investigated miRNA-miRNA cooperative regulatory landscape across 18 cancer types and summar...

    journal_title:Briefings in bioinformatics

    pub_type: 杂志文章,评审

    doi:10.1093/bib/bby038

    authors: Shao T,Wang G,Chen H,Xie Y,Jin X,Bai J,Xu J,Li X,Huang J,Jin Y,Li Y

    更新日期:2019-09-27 00:00:00