Abstract:
:Evaluation of the functional impact of cancer-associated missense variants is more difficult than for protein-truncating mutations and consequently standard guidelines for the interpretation of sequence variants have been recently proposed. A number of algorithms and software products were developed to predict the impact of cancer-associated missense mutations on protein structure and function. Importantly, direct assessment of the variants using high-throughput functional assays using simple genetic systems can help in speeding up the functional evaluation of newly identified cancer-associated variants. We developed the web tool CRIMEtoYHU (CTY) to help geneticists in the evaluation of the functional impact of cancer-associated missense variants. Humans and the yeast Saccharomyces cerevisiae share thousands of protein-coding genes although they have diverged for a billion years. Therefore, yeast humanization can be helpful in deciphering the functional consequences of human genetic variants found in cancer and give information on the pathogenicity of missense variants. To humanize specific positions within yeast genes, human and yeast genes have to share functional homology. If a mutation in a specific residue is associated with a particular phenotype in humans, a similar substitution in the yeast counterpart may reveal its effect at the organism level. CTY simultaneously finds yeast homologous genes, identifies the corresponding variants and determines the transferability of human variants to yeast counterparts by assigning a reliability score (RS) that may be predictive for the validity of a functional assay. CTY analyzes newly identified mutations or retrieves mutations reported in the COSMIC database, provides information about the functional conservation between yeast and human and shows the mutation distribution in human genes. CTY analyzes also newly found mutations and aborts when no yeast homologue is found. Then, on the basis of the protein domain localization and functional conservation between yeast and human, the selected variants are ranked by the RS. The RS is assigned by an algorithm that computes functional data, type of mutation, chemistry of amino acid substitution and the degree of mutation transferability between human and yeast protein. Mutations giving a positive RS are highly transferable to yeast and, therefore, yeast functional assays will be more predictable. To validate the web application, we have analyzed 8078 cancer-associated variants located in 31 genes that have a yeast homologue. More than 50% of variants are transferable to yeast. Incidentally, 88% of all transferable mutations have a reliability score >0. Moreover, we analyzed by CTY 72 functionally validated missense variants located in yeast genes at positions corresponding to the human cancer-associated variants. All these variants gave a positive RS. To further validate CTY, we analyzed 3949 protein variants (with positive RS) by the predictive algorithm PROVEAN. This analysis shows that yeast-based functional assays will be more predictable for the variants with positive RS. We believe that CTY could be an important resource for the cancer research community by providing information concerning the functional impact of specific mutations, as well as for the design of functional assays useful for decision support in precision medicine.
journal_name
FEMS Yeast Resjournal_title
FEMS yeast researchauthors
Mercatanti A,Lodovichi S,Cervelli T,Galli Adoi
10.1093/femsyr/fox078subject
Has Abstractpub_date
2017-12-01 00:00:00issue
8eissn
1567-1356issn
1567-1364pii
4562592journal_volume
17pub_type
杂志文章abstract::The transcriptional response of laboratory strains of Saccharomyces cerevisiae to salt or sorbitol stress has been well studied. These studies have yielded valuable data on how the yeast adapts to these stress conditions. However, S. cerevisiae is a saccharophilic fungus and in its natural environment this yeast encou...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/S1567-1356(02)00203-9
更新日期:2003-06-01 00:00:00
abstract::The budding yeast, Saccharomyces cerevisiae, is an efficient model for studying oxidative stress, programmed cell death and aging. The present study was carried out to investigate antioxidant, the anti-apoptotic and anti-aging activity of a natural compound, astaxanthin, in S. cerevisiae model. The survivability of ye...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/foy113
更新日期:2019-01-01 00:00:00
abstract::In the macroscopic world, ecological interactions between multiple species of fauna and flora are recognised as major role-players in the evolution of any particular species. By comparison, research on ecological interactions as a driver of evolutionary adaptation in microbial ecosystems has been neglected. The evolut...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1093/femsyr/foz072
更新日期:2019-11-01 00:00:00
abstract::The durum wheat TMKP1 gene encodes a MAP kinase phosphatase. When overexpressed in Saccharomyces cerevisiae, TMKP1 leads to salt stress tolerance (especially LiCl ), which is dependent on the phosphatase activity of the protein. The TMKP1-associated Li(+) resistance is restricted to a galactose-containing medium. Inte...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2012.00827.x
更新日期:2012-11-01 00:00:00
abstract::Killer-toxin complexes produced by Kluyveromyces lactis and Pichia acaciae inhibit cell proliferation of Saccharomyces cerevisiae. Analysis of their actions in haploid MATalpha cells revealed that introduction of the opposite mating-type locus (MATa) significantly suppressed antizymosis. Together with resistance expre...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2005.00006.x
更新日期:2006-05-01 00:00:00
abstract::In vivo assembly of overlapping fragments by homologous recombination in Saccharomyces cerevisiae is a powerful method to engineer large DNA constructs. Whereas most in vivo assembly methods reported to date result in circular vectors, stable integrated constructs are often preferred for metabolic engineering as they ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12087
更新日期:2013-12-01 00:00:00
abstract::Many of the difficulties of studying evolution in action can be surmounted using populations of microorganisms, such as yeast. A readily manipulated sexual system and an increasingly sophisticated array of molecular and genomic tools uniquely qualify Saccharomyces cerevisiae as an experimental subject. This minireview...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1111/j.1567-1364.2006.00061.x
更新日期:2006-08-01 00:00:00
abstract::We have cloned the Hansenula polymorpha SWI1 and SNF2 genes by functional complementation of mutants that are defective in methanol utilisation. These genes encode proteins similar to Saccharomyces cerevisiae Swi1p and Snf2p, which are subunits of the SWI/SNF complex. This complex belongs to the family of nucleosome-r...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/j.femsyr.2004.01.009
更新日期:2004-05-01 00:00:00
abstract::The feasibility of using a single vector to clone a cytochrome P450 monooxygenase (P450) in different yeasts and then compare whole-cell hydroxylase activity was investigated. A broad-range yeast expression vector using the ylTEFp to drive expression of the cloned gene and the scTEFp to drive the hygromycin resistance...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12142
更新日期:2014-06-01 00:00:00
abstract::To analyse the reliability and accuracy of genotype analysis with high-density oligonucleotide microarrays, this method and other experimental approaches were used to analyse genomic DNA of two popular Saccharomyces cerevisiae laboratory strains. S288C was used for systematic sequencing of 'the' S. cerevisiae genome; ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/S1567-1356(03)00156-9
更新日期:2003-12-01 00:00:00
abstract::Yarrowia lipolytica is a dimorphic fungus whose morphology is controlled by several factors such as pH and different compounds. To determine if the STE11-mitogen-activated protein kinase (MAPK) pathway plays a role in dimorphism of Y. lipolytica, we isolated the gene encoding a Mapkkk. The isolated gene (STE11) has an...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2006.00084.x
更新日期:2006-08-01 00:00:00
abstract::Proteostasis is a cellular housekeeping process that refers to the healthy maintenance of the cellular proteome that governs the fate of proteins from synthesis to degradation. Perturbations of proteostasis might result in protein dysfunction with consequent deleterious effects that can culminate in cell death. To dea...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1093/femsyr/foy043
更新日期:2018-08-01 00:00:00
abstract::Development of a pulsed-light (PL) approach to inanimate surface decontamination is timely, as the incidence of yeast-related infections in healthcare remains unacceptably high. Critical electrical and biological factors governing the efficacy of PL for the in vitro inactivation of medically important yeast were estab...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2009.00543.x
更新日期:2009-09-01 00:00:00
abstract::The biosynthesis of yeast phosphatidylglycerol (PG) takes place in the inner mitochondrial membrane. Outside mitochondria, the abundance of PG is low. Here, we present evidence that the subcellular distribution of PG is maintained by the locally controlled enzymatic activity of the PG-specific phospholipase, Pgc1. A f...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/foz045
更新日期:2019-08-01 00:00:00
abstract::Screening for genes affecting super-secreting phenotype of the over-secreting mutant of Kluyveromyces lactis resulted in isolation of the gene named KlMNN10, sharing high homology with Saccharomyces cerevisiae MNN10. The disruption of the KlMNN10 in Kluyveromyces lactis, as well as of MNN10 and MNN11 in Saccharomyces ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/j.femsyr.2004.03.001
更新日期:2004-09-01 00:00:00
abstract::d-Amino acid oxidase (DAO) is an important flavo-enzyme that catalyzes the oxidative deamination of d-amino acids into the corresponding alpha-keto acid, ammonia and H(2)O(2). We identified two amino acid oxidases in the methylotrophic yeast Pichia pastoris: Dao1p, which preferentially uses d-alanine as a substrate, a...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2010.00647.x
更新日期:2010-09-01 00:00:00
abstract::The Tapirapé people of the Tapi'itãwa tribe of Brazil produce several fermented foods and beverages, one of which is called 'cauim'. This beverage usually makes up the main staple food for adults and children. Several substrates are used in its production, including cassava, rice, corn, maize and peanuts. A fermentati...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2007.00241.x
更新日期:2007-09-01 00:00:00
abstract::Secondary metabolites are an important source of high-value chemicals, many of which exhibit important pharmacological properties. These valuable natural products are often difficult to synthesize chemically and are commonly isolated through inefficient extractions from natural biological sources. As such, they are in...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1111/j.1567-1364.2011.00774.x
更新日期:2012-03-01 00:00:00
abstract::The amplification by PCR of the Intergenic Spacer region (IGS) of rDNA followed by Restriction Fragment Length Polymorphism (RFLP) analysis was evaluated as a potential method for the identification of Debaryomyces hansenii among other yeast species that frequently contaminate Intermediate-Moisture Foods (IMFs). For a...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/j.femsyr.2004.09.002
更新日期:2005-02-01 00:00:00
abstract::Cadmium ions disrupt reactive oxygen species/Ca(2+) homeostasis and subsequently elicit cell death and adaptive signaling cascades in eukaryotic cells. Through a functional genomics approach, we have identified deletion mutants of 106 yeast genes, including three MAP kinase genes (HOG1, SLT2, and KSS1), are sensitive ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/1567-1364.12220
更新日期:2014-12-01 00:00:00
abstract::The opportunistic human fungal pathogen Candida glabrata is second only to C. albicans as the cause of Candida infections and yet is more closely related to Saccharomyces cerevisiae. Recent advances in functional genomics technologies and computational approaches to decipher regulatory networks, and the comparison of ...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1093/femsyr/fov087
更新日期:2015-12-01 00:00:00
abstract::Trk1 and Trk2 are the major K(+) transport systems in Schizosaccharomyces pombe. Both transporters individually seem to be able to cope with K(+) requirements of the cells under normal conditions, since only the double mutant shows defective K(+) transport and defective growth at limiting K(+) concentrations. We have ...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1016/j.femsyr.2003.11.003
更新日期:2004-03-01 00:00:00
abstract::A new, heat shock-inducible expression system based on an endogenous hsp16+ promoter was developed for use in the fission yeast Schizosaccharomyces pombe. Analysis of GFP expression profiles indicated that a 1.2-kb segment of the hsp16+ promoter region was sufficient to drive expression of heterologous protein. The hs...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2006.00093.x
更新日期:2006-09-01 00:00:00
abstract::The progenitor of the Dekkera/Brettanomyces clade separated from the Saccharomyces/Kluyveromyces clade over 200 million years ago. However, within both clades, several lineages developed similar physiological traits. Both Saccharomyces cerevisiae and Dekkera bruxellensis are facultative anaerobes; in the presence of e...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2010.00644.x
更新日期:2010-08-01 00:00:00
abstract::This study displays a screening using yeast strains deficient in protein kinases known to exist in Saccharomyces cerevisiae. From 95 viable single mutants, 20 mutants appear to be affected in the glucose-induced extracellular acidification. The mutants that are unaffected in calcium signaling were tested for their sen...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/fov003
更新日期:2015-03-01 00:00:00
abstract::We used multi-locus sequence typing (MLST) to investigate 35 yeast isolates representing the two genome-sequenced strains plus the type strain of Candida albicans, four isolates originally identified as Candida stellatoidea type I and 28 representing type strains of other species now regarded as synonymous with C. alb...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2008.00392.x
更新日期:2008-08-01 00:00:00
abstract::Maintenance and adaptation of energy metabolism could play an important role in the cellular ability to respond to DNA damage. A large number of studies suggest that the sensitivity of cells to oxidants and oxidative stress depends on the activity of cellular metabolism and is dependent on the glucose concentration. I...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2009.00505.x
更新日期:2009-06-01 00:00:00
abstract::Formic acid disrupts mitochondrial electron transport and sequentially causes cell death in mammalian ocular cells by an unidentified molecular mechanism. Here, we show that a low concentration of formic acid induces apoptosis-like cell death in the budding yeast Saccharomyces cerevisiae, with several morphological an...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1111/j.1567-1364.2008.00375.x
更新日期:2008-06-01 00:00:00
abstract::Early screens in yeast for mutations exhibiting sensitivity to DNA damage identified nuclear pore components, but their role in DNA repair was not well understood. Over the last decade, studies have revealed that several types of persistent DNA lesions relocate to either the nuclear pore complex (NPC) or nuclear envel...
journal_title:FEMS yeast research
pub_type: 杂志文章,评审
doi:10.1093/femsyr/fow095
更新日期:2016-12-01 00:00:00
abstract::Eight yeast strains that asexually reproduce by cell fission were isolated from bee bread of different solitary bees in Germany. DNA sequence analysis revealed that the strains shared the same sequence in the D1/D2 domain of the nuclear large subunit (LSU) rRNA gene with a strain that was previously isolated from a fi...
journal_title:FEMS yeast research
pub_type: 杂志文章
doi:10.1093/femsyr/foz038
更新日期:2019-06-01 00:00:00