Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene

Murillo, Javier; Spetale, Flavio; Guillaume, Serge; Bulacio, Pilar; Garcia Labari, Ignacio; Cailloux, Olivier; Destercke, Sebastien; Tapia, Elizabeth

doi:10.3390/biom10030475

Open AccessArticle

Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene

by

Javier Murillo

^1,*,

Flavio Spetale

¹

,

Serge Guillaume

²

,

Pilar Bulacio

¹,

Ignacio Garcia Labari

¹,

Olivier Cailloux

³,

Sebastien Destercke

⁴ and

Elizabeth Tapia

¹

Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas (CIFASIS-CONICET), Universidad Nacional de Rosario, CP 2000 Rosario, Santa Fe, Argentina

²

ITAP, Univ Montpellier, INRAE, Montpellier SupAgro, Montpellier, France

³

Université Paris-Dauphine, Université PSL, CNRS, LAMSADE, 75016 Paris, France

⁴

Université de Technologie de Compiegne, 60200 Compiegne, France

^*

Author to whom correspondence should be addressed.

Biomolecules 2020, 10(3), 475; https://doi.org/10.3390/biom10030475

Submission received: 29 November 2019 / Revised: 15 January 2020 / Accepted: 29 January 2020 / Published: 20 March 2020

(This article belongs to the Special Issue Bioinformatics and Precision Computational Biology: Selected Papers from the X International Conference on Bioinformatics #SoIBio+10)

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Abstract

Single nucleotide variants (SNVs) occurring in a protein coding gene may disrupt its function in multiple ways. Predicting this disruption has been recognized as an important problem in bioinformatics research. Many tools, hereafter p-tools, have been designed to perform these predictions and many of them are now of common use in scientific research, even in clinical applications. This highlights the importance of understanding the semantics of their outputs. To shed light on this issue, two questions are formulated, (i) do p-tools provide similar predictions? (inner consistency), and (ii) are these predictions consistent with the literature? (outer consistency). To answer these, six p-tools are evaluated with exhaustive SNV datasets from the BRCA1 gene. Two indices, called

K_{a l l}

and

K_{s t r o n g}

, are proposed to quantify the inner consistency of pairs of p-tools while the outer consistency is quantified by standard information retrieval metrics. While the inner consistency analysis reveals that most of the p-tools are not consistent with each other, the outer consistency analysis reveals they are characterized by a low prediction performance. Although this result highlights the need of improving the prediction performance of individual p-tools, the inner consistency results pave the way to the systematic design of truly diverse ensembles of p-tools that can overcome the limitations of individual members.

Keywords: SNV; prediction tools; BRCA1 gene; consistency of tools; preference relations

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MDPI and ACS Style

Murillo, J.; Spetale, F.; Guillaume, S.; Bulacio, P.; Garcia Labari, I.; Cailloux, O.; Destercke, S.; Tapia, E. Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene. Biomolecules 2020, 10, 475. https://doi.org/10.3390/biom10030475

AMA Style

Murillo J, Spetale F, Guillaume S, Bulacio P, Garcia Labari I, Cailloux O, Destercke S, Tapia E. Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene. Biomolecules. 2020; 10(3):475. https://doi.org/10.3390/biom10030475

Chicago/Turabian Style

Murillo, Javier, Flavio Spetale, Serge Guillaume, Pilar Bulacio, Ignacio Garcia Labari, Olivier Cailloux, Sebastien Destercke, and Elizabeth Tapia. 2020. "Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene" Biomolecules 10, no. 3: 475. https://doi.org/10.3390/biom10030475

APA Style

Murillo, J., Spetale, F., Guillaume, S., Bulacio, P., Garcia Labari, I., Cailloux, O., Destercke, S., & Tapia, E. (2020). Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene. Biomolecules, 10(3), 475. https://doi.org/10.3390/biom10030475

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Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene

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