Branding/Logomark minus Citation Combined Shape Icon/Bookmark-empty Icon/Copy Icon/Collection Icon/Close Copy 7 no author result Created with Sketch. Icon/Back Created with Sketch. Match!

Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods

Published on Mar 6, 2006in Nucleic Acids Research 11.15
· DOI :10.1093/nar/gkj518
Ewy Mathé18
Estimated H-index: 18
(IARC: International Agency for Research on Cancer),
Magali Olivier33
Estimated H-index: 33
(IARC: International Agency for Research on Cancer)
+ 3 AuthorsSean V. Tavtigian55
Estimated H-index: 55
(IARC: International Agency for Research on Cancer)
Cite
Abstract
Prediction of the biological effect of missense substitutions has become important because they are often observed in known or candidate disease susceptibility genes. In this paper, we carried out a 3-step analysis of 1514 missense substitutions in the DNA-binding domain (DBD) of TP53, the most frequently mutated gene in human cancers. First, we calculated two types of conservation scores based on a TP53 multiple sequence alignment (MSA) for each substitution: (i) Grantham Variation (GV), which measures the degree of biochemical variation among amino acids found at a given position in the MSA; (ii) Grantham Deviation (GD), which reflects the ‘biochemical distance’ of the mutant amino acid from the observed amino acid at a particular position (given by GV). Second, we used a method that combines GV and GD scores, Align-GVGD, to predict the transactivation activity of each missense substitution. We compared our predictions against experimentally measured transactivation activity (yeast assays) to evaluate their accuracy. Finally, the prediction results were compared with those obtained by the program Sorting Intolerant from Tolerant (SIFT) and Dayhoff's classification. Our predictions yielded high prediction accuracy for mutants showing a loss of transactivation (∼88% specificity) with lower prediction accuracy for mutants with transactivation similar to that of the wild-type (67.9 to 71.2% sensitivity). Align-GVGD results were comparable to SIFT (88.3 to 90.6% and 67.4 to 70.3% specificity and sensitivity, respectively) and outperformed Dayhoff's classification (80 and 40.9% specificity and sensitivity, respectively). These results further demonstrate the utility of the Align-GVGD method, which was previously applied to BRCA1. Align-GVGD is available online at http://agvgd.iarc.fr.
  • References (32)
  • Citations (221)
Cite
References32
Newest
Published on Sep 9, 2005in Journal of Medical Genetics 5.90
Sean V. Tavtigian55
Estimated H-index: 55
(IARC: International Agency for Research on Cancer),
Amie M. Deffenbaugh18
Estimated H-index: 18
(Myriad Genetics)
+ 6 AuthorsAurélie Thomas1
Estimated H-index: 1
Background: Genetic testing for hereditary cancer syndromes contributes to the medical management of patients who may be at increased risk of one or more cancers. BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer is one such widely used test. However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions. Methods: We developed an extension of the Grantham difference, called A...
Published on May 1, 2004in Journal of Molecular Biology 5.07
Orla O'Sullivan33
Estimated H-index: 33
(UCD: University College Dublin),
Karsten Suhre54
Estimated H-index: 54
(CNRS: Centre national de la recherche scientifique)
+ 2 AuthorsCedric Notredame40
Estimated H-index: 40
(Swiss Institute of Bioinformatics)
Most bioinformatics analyses require the assembly of a multiple sequence alignment. It has long been suspected that structural information can help to improve the quality of these alignments, yet the effect of combining sequences and structures has not been evaluated systematically. We developed 3DCoffee, a novel method for combining protein sequences and structures in order to generate high-quality multiple sequence alignments. 3DCoffee is based on TCoffee version 2.00, and uses a mixture of pa...
Published on Jan 1, 2004in Nucleic Acids Research 11.15
Nathan O. Stitziel3
Estimated H-index: 3
(UIC: University of Illinois at Chicago),
T. Andrew Binkowski13
Estimated H-index: 13
(UIC: University of Illinois at Chicago)
+ 2 AuthorsJie Liang35
Estimated H-index: 35
The database of topographic mapping of Single Nucleotide Polymorphism (topoSNP) provides an online resource for analyzing non-synonymous SNPs (nsSNPs) that can be mapped onto known 3D structures of proteins. These include disease- associated nsSNPs derived from the Online Mendelian Inheritance in Man (OMIM) database and other nsSNPs derived from dbSNP, a resource at the National Center for Biotechnology Information that catalogs SNPs. TopoSNP further classifies each nsSNP site into three categor...
Published on Oct 30, 2003in Genome Biology 14.03
Dennis Vitkup31
Estimated H-index: 31
(Harvard University),
Chris Sander C130
Estimated H-index: 130
(MIT: Massachusetts Institute of Technology)
+ 0 AuthorsGeorge M Church G M135
Estimated H-index: 135
(Harvard University)
Background Nonsynonymous mutations in the coding regions of human genes are responsible for phenotypic differences between humans and for susceptibility to genetic disease. Computational methods were recently used to predict deleterious effects of nonsynonymous human mutations and polymorphisms. Here we focus on understanding the amino-acid mutation spectrum of human genetic disease. We compare the disease spectrum to the spectra of mutual amino-acid mutation frequencies, non-disease polymorphis...
Shunsuke Kato21
Estimated H-index: 21
,
Shuang-Yin Han7
Estimated H-index: 7
+ 4 AuthorsChikashi Ishioka34
Estimated H-index: 34
Inactivation of the tumor suppressor p53 by missense mutations is the most frequent genetic alteration in human cancers. The common missense mutations in the TP53 gene disrupt the ability of p53 to bind to DNA and consequently to transactivate downstream genes. However, it is still not fully understood how a large number of the remaining mutations affect p53 structure and function. Here, we used a comprehensive site-directed mutagenesis technique and a yeast-based functional assay to construct, ...
Published on Jun 1, 2003in Human Mutation 4.45
Peter D. Stenson40
Estimated H-index: 40
(University of Wales),
Edward V. Ball26
Estimated H-index: 26
(University of Wales)
+ 6 AuthorsDavid Neil Cooper89
Estimated H-index: 89
(University of Wales)
The Human Gene Mutation Database (HGMD) constitutes a comprehensive core collection of data on germ-line mutations in nuclear genes underlying or associated with human inherited disease (www.hgmd.org). Data catalogued includes: single base-pair substitutions in coding, regulatory and splicing-relevant regions; micro-deletions and micro-insertions; indels; triplet repeat expansions as well as gross deletions; insertions; duplications; and complex rearrangements. Each mutation is entered into HGMD...
Published on Feb 1, 2003in Oncogene 6.63
Marc S. Greenblatt29
Estimated H-index: 29
(UVM: University of Vermont),
J G Beaudet1
Estimated H-index: 1
(UVM: University of Vermont)
+ 4 AuthorsJeffrey P. Bond25
Estimated H-index: 25
(UVM: University of Vermont)
Detailed computational study of p53 and p16 : using evolutionary sequence analysis and disease-associated mutations to predict the functional consequences of allelic variants
Published on Jan 1, 2003
Peter D. Stenson40
Estimated H-index: 40
,
Edward V. Ball26
Estimated H-index: 26
+ 5 AuthorsDavid Neil Cooper89
Estimated H-index: 89
Published on Sep 1, 2002in Nucleic Acids Research 11.15
Vasily Ramensky19
Estimated H-index: 19
,
Peer Bork170
Estimated H-index: 170
,
Shamil R. Sunyaev64
Estimated H-index: 64
Human single nucleotide polymorphisms (SNPs) represent the most frequent type of human population DNA variation. One of the main goals of SNP research is to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. Non-synonymous coding SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions, are believed to have the highest impact on phenotype. Here we present a World Wide Web server to predict the effect o...
Published on Jun 1, 2002in Human Mutation 4.45
Magali Olivier33
Estimated H-index: 33
(IARC: International Agency for Research on Cancer),
Rosalind Eeles88
Estimated H-index: 88
+ 3 AuthorsPierre Hainaut78
Estimated H-index: 78
(IARC: International Agency for Research on Cancer)
The IARC TP53 database: New Online mutation analysis and recommendations to users Mutations in the tumor suppressor gene TP53 are frequent in most human cancers. Comparison of the mutation patterns in different cancers may reveal clues on the natural history of the disease. Over the past 10 years, several databases of TP53 mutations have been developed. The most extensive of these databases is maintained and developed at the International Agency for Research on Cancer. The database compiles all ...
Cited By221
Newest
Published on Dec 1, 2019in Scientific Reports 4.01
Sami Belhadj2
Estimated H-index: 2
,
Isabel Quintana1
Estimated H-index: 1
+ 10 AuthorsVictor Moreno55
Estimated H-index: 55
The cancer-predisposing syndrome caused by biallelic mutations in NTHL1 may not be a solely colorectal cancer (CRC) and polyposis syndrome but rather a multi-tumor recessive disease. The presence of ≤10 adenomas in several mutation carriers suggests a possible causal role of NTHL1 in hereditary or early-onset nonpolyposis CRC. The involvement of NTHL1 in serrated/hyperplastic polyposis remains unexplored. The aim of our study is to elucidate the role of NTHL1 in the predisposition to personal or...
Published on Feb 4, 2019in Scientific Reports 4.01
Cathrine Jespersgaard4
Estimated H-index: 4
(UCPH: University of Copenhagen),
Cathrine Jespersgaard (UCPH: University of Copenhagen)+ 11 AuthorsLanlan Dai5
Estimated H-index: 5
Inherited retinal diseases (IRDs) are a common cause of visual impairment. IRD covers a set of genetically highly heterogeneous disorders with more than 150 genes associated with one or more clinical forms of IRD. Molecular genetic diagnosis has become increasingly important especially due to expanding number of gene therapy strategies under development. Next generation sequencing (NGS) of gene panels has proven a valuable diagnostic tool in IRD. We present the molecular findings of 677 individu...
Published on Jun 26, 2019in Human Mutation 4.45
Alin Voskanian (UMBC: University of Maryland, Baltimore County), Panagiotis Katsonis11
Estimated H-index: 11
(BCM: Baylor College of Medicine)
+ 26 AuthorsMax Miller (RU: Rutgers University)
Published on Apr 8, 2019in Journal of Medical Genetics 5.90
Amanda B. Spurdle61
Estimated H-index: 61
,
Stephanie Greville-Heygate3
Estimated H-index: 3
+ 18 AuthorsHelen V. Firth41
Estimated H-index: 41
The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease use...
Published on Jun 1, 2019in Human Mutation 4.45
Cristina Fortuno2
Estimated H-index: 2
,
Arcadi Cipponi3
Estimated H-index: 3
+ 9 AuthorsDavid M. Thomas49
Estimated H-index: 49
Published on May 8, 2019in Molecular Genetics & Genomic Medicine
George G. Schweitzer7
Estimated H-index: 7
(WashU: Washington University in St. Louis),
Connie Gan1
Estimated H-index: 1
(WashU: Washington University in St. Louis)
+ 5 AuthorsRita T. Brookheart5
Estimated H-index: 5
(WashU: Washington University in St. Louis)
Published on May 1, 2019in Human Mutation 4.45
Angeliki Delimitsou1
Estimated H-index: 1
,
Florentia Fostira16
Estimated H-index: 16
+ 8 AuthorsGerassimos E. Voutsinas3
Estimated H-index: 3
Published on Mar 29, 2019in Journal of Molecular Cell Biology 4.67
Arnold J. Levine123
Estimated H-index: 123
(IAS: Institute for Advanced Study)
Published on Mar 20, 2019in The Scientific World Journal
Vera G. Pshennikova2
Estimated H-index: 2
(North-Eastern Federal University),
Nikolay A. Barashkov6
Estimated H-index: 6
(North-Eastern Federal University)
+ 12 AuthorsNikolay N. Sazonov2
Estimated H-index: 2
(North-Eastern Federal University)
In silico predictive software allows assessing the effect of amino acid substitutions on the structure or function of a protein without conducting functional studies. The accuracy of in silico pathogenicity prediction tools has not been previously assessed for variants associated with autosomal recessive deafness 1A (DFNB1A). Here, we identify in silico tools with the most accurate clinical significance predictions for missense variants of the GJB2 (Cx26), GJB6 (Cx30), and GJB3 (Cx31) connexin g...
Published on Dec 1, 2018in BMC Cancer 2.93
Yong Alison Wang1
Estimated H-index: 1
,
Jhih-Wei Jian4
Estimated H-index: 4
(AS: Academia Sinica)
+ 4 AuthorsAn-Suei Yang34
Estimated H-index: 34
(AS: Academia Sinica)
Background It is unclear whether germline breast cancer susceptibility gene mutations affect breast cancer related outcomes. We wanted to evaluate mutation patterns in 20 breast cancer susceptibility genes and correlate the mutations with clinical characteristics to determine the effects of these germline mutations on breast cancer prognosis.