Assessment of patient clinical descriptions and pathogenic variants from gene panel sequences in the CAGI-5 intellectual disability challenge

被引：12

作者：

Carraro, Marco ^{[1
]}

Monzon, Alexander Miguel ^{[1
]}

Chiricosta, Luigi ^{[1
]}

Reggiani, Francesco ^{[1
,2
]}

Aspromonte, Maria Cristina ^{[3
]}

Bellini, Mariagrazia ^{[3
,4
]}

Pagel, Kymberleigh ^{[5
]}

Jiang, Yuxiang ^{[5
]}

Radivojac, Predrag ^{[5
]}

Kundu, Kunal ^{[6
,7
]}

Pal, Lipika R. ^{[6
]}

Yin, Yizhou ^{[6
,7
]}

Limongelli, Ivan ^{[8
]}

Andreoletti, Gaia ^{[6
,9
]}

Moult, John ^{[6
,9
]}

Wilson, Stephen J. ^{[10
]}

Katsonis, Panagiotis ^{[10
]}

Lichtarge, Olivier ^{[10
]}

Chen, Jingqi ^{[11
]}

Wang, Yaqiong ^{[11
]}

Hu, Zhiqiang ^{[11
]}

Brenner, Steven E. ^{[11
]}

Ferrari, Carlo ^{[2
]}

Murgia, Alessandra ^{[3
,4
]}

Tosatto, Silvio C. E. ^{[1
,12
]}

Leonardi, Emanuela ^{[3
,4
]}

机构：

[1] Univ Padua, Dept Biomed Sci, Viale G Colombo 3, I-35131 Padua, Italy

[2] Univ Padua, Dept Informat Engn, Padua, Italy

[3] Univ Padua, Dept Woman & Child Hlth, Corso Stati Uniti 4, I-35127 Padua, Italy

[4] Fdn Ist Ric Pediat IRP, Padua, Italy

[5] Northeastern Univ, Khoury Coll Comp & Informat Sci, Boston, MA 02115 USA

[6] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD USA

[7] Univ Maryland, Biol Sci Grad Program, Computat Biol Bioinformat & Genom, College Pk, MD 20742 USA

[8] EnGenome Srl, Via Ferrata 5, Pavia, Italy

[9] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[10] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[11] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA

[12] CNR, Natl Res Council, Inst Neurosci, Padua, Italy

来源：

HUMAN MUTATION | 2019年 / 40卷 / 09期

关键词：

community challenge; critical assessment; genetic testing; phenotype prediction; variant interpretation; AUTISM SPECTRUM DISORDERS; CLINVAR PUBLIC ARCHIVE; MUTATION DATABASE; CONVERGENCE; PREDICTION; LESSONS;

D O I：

10.1002/humu.23823

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The Critical Assessment of Genome Interpretation-5 intellectual disability challenge asked to use computational methods to predict patient clinical phenotypes and the causal variant(s) based on an analysis of their gene panel sequence data. Sequence data for 74 genes associated with intellectual disability (ID) and/or autism spectrum disorders (ASD) from a cohort of 150 patients with a range of neurodevelopmental manifestations (i.e. ID, autism, epilepsy, microcephaly, macrocephaly, hypotonia, ataxia) have been made available for this challenge. For each patient, predictors had to report the causative variants and which of the seven phenotypes were present. Since neurodevelopmental disorders are characterized by strong comorbidity, tested individuals often present more than one pathological condition. Considering the overall clinical manifestation of each patient, the correct phenotype has been predicted by at least one group for 93 individuals (62%). ID and ASD were the best predicted among the seven phenotypic traits. Also, causative or potentially pathogenic variants were predicted correctly by at least one group. However, the prediction of the correct causative variant seems to be insufficient to predict the correct phenotype. In some cases, the correct prediction has been supported by rare or common variants in genes different from the causative one.

引用

页码：1330 / 1345

页数：16

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