KEGG as a reference resource for gene and protein annotation

Kanehisa, Minoru; Sato, Yoko; Kawashima, Masayuki; Furumichi, Miho; Tanabe, Mikio

doi:10.1093/nar/gkv1070

Cited by 5,744 publications

(4,898 citation statements)

References 14 publications

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“…52 As shown in Figure S4A, we found that the most significantly enriched pathway was related to metabolism, specifically drug and xenobiotic metabolism (p value ¼ 2.30 3 10 À6 ), which is a key function of the kidney tubules. The full list of the GO results is in Table S6.…”

Section: Validation and Replication Of Kidney Cis-eqtl Signalsmentioning

confidence: 79%

Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease

Qiu

et al. 2017

The American Journal of Human Genetics

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Chronic kidney disease (CKD) is a complex gene-environmental disease affecting close to 10% of the US population. Genome-wide association studies (GWASs) have identified sequence variants, localized to non-coding genomic regions, associated with kidney function. Despite these robust observations, the mechanism by which variants lead to CKD remains a critical unanswered question. Expression quantitative trait loci (eQTL) analysis is a method to identify genetic variation associated with gene expression changes in specific tissue types. We hypothesized that an integrative analysis combining CKD GWAS and kidney eQTL results can identify candidate genes for CKD. We performed eQTL analysis by correlating genotype with RNA-seq-based gene expression levels in 96 human kidney samples. Applying stringent statistical criteria, we detected 1,886 genes whose expression differs with the sequence variants. Using direct overlap and Bayesian methods, we identified new potential target genes for CKD. With respect to one of the target genes, lysosomal beta A mannosidase (MANBA), we observed that genetic variants associated with MANBA expression in the kidney showed statistically significant colocalization with variants identified in CKD GWASs, indicating that MANBA is a potential target gene for CKD. The expression of MANBA was significantly lower in kidneys of subjects with risk alleles. Suppressing manba expression in zebrafish resulted in renal tubule defects and pericardial edema, phenotypes typically induced by kidney dysfunction. Our analysis shows that gene-expression changes driven by genetic variation in the kidney can highlight potential new target genes for CKD development.

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Section: Validation and Replication Of Kidney Cis-eqtl Signalsmentioning

confidence: 79%

Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease

Qiu

et al. 2017

The American Journal of Human Genetics

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“…To uncover the putative functional role of the highly differentiated SNPs, we used SNPeff 4.3 (Cingolani et al., 2012) and the NCBI honeybee annotation version 102 (Pruitt et al., 2013). Subsequently, we performed a gene ontology (GO) analysis in the DAVID v.8.0 database (Huang, Sherman, & Lempicki, 2009) considering the GO terms of the biological process (BP), molecular function (MF), cellular component (CC) (Gene Ontology Consortium, 2015) and the KEGG pathway (Kanehisa, Sato, Kawashima, Furumichi, & Tanabe, 2016). …”

Section: Methodsmentioning

confidence: 99%

Developing reduced SNP assays from whole‐genome sequence data to estimate introgression in an organism with complex genetic patterns, the Iberian honeybee (Apis mellifera iberiensis)

Henriques

Parejo

Vignal

et al. 2018

Evolutionary Applications

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The most important managed pollinator, the honeybee (Apis mellifera L.), has been subject to a growing number of threats. In western Europe, one such threat is large‐scale introductions of commercial strains (C‐lineage ancestry), which is leading to introgressive hybridization and even the local extinction of native honeybee populations (M‐lineage ancestry). Here, we developed reduced assays of highly informative SNPs from 176 whole genomes to estimate C‐lineage introgression in the most diverse and evolutionarily complex subspecies in Europe, the Iberian honeybee (Apis mellifera iberiensis). We started by evaluating the effects of sample size and sampling a geographically restricted area on the number of highly informative SNPs. We demonstrated that a bias in the number of fixed SNPs (FST = 1) is introduced when the sample size is small (N ≤ 10) and when sampling only captures a small fraction of a population's genetic diversity. These results underscore the importance of having a representative sample when developing reliable reduced SNP assays for organisms with complex genetic patterns. We used a training data set to design four independent SNP assays selected from pairwise FST between the Iberian and C‐lineage honeybees. The designed assays, which were validated in holdout and simulated hybrid data sets, proved to be highly accurate and can be readily used for monitoring populations not only in the native range of A. m. iberiensis in Iberia but also in the introduced range in the Balearic islands, Macaronesia and South America, in a time‐ and cost‐effective manner. While our approach used the Iberian honeybee as model system, it has a high value in a wide range of scenarios for the monitoring and conservation of potentially hybridized domestic and wildlife populations.

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“…9). This pathway is associated with thermal hypersensitivity and may be involved in persistent pain responses 41 , and does not appear to be associated with convergent adaptations between the thylacine and canids. Thus, it appears that selection on genes in conserved pathways is very limited and unlikely to be relevant to convergence.…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

“…Alternatively, selection in these lineages may have targeted different genes involved in similar biological processes. Therefore, we performed a KEGG pathway analysis 41 of thylacine and canid positively selected genes using Enrichr 42 . We identified one pathway, inflammatory mediator regulation of TRP channels (hsa04750), among the top terms in both canids and the thylacine (Supplementary Tables 19 and 20).…”

Section: Nature Ecology and Evolutionmentioning

confidence: 99%

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

et al. 2017

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The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids. Retroposon insertion patterns placed the thylacine as the basal lineage in Dasyuromorphia and suggest incomplete lineage sorting in early dasyuromorphs. Demographic analysis indicated a long-term decline in genetic diversity starting well before the arrival of humans in Australia. In spite of their extraordinary phenotypic convergence, comparative genomic analyses demonstrated that amino acid homoplasies between the thylacine and canids are largely consistent with neutral evolution. Furthermore, the genes and pathways targeted by positive selection differ markedly between these species. Together, these findings support models of adaptive convergence driven primarily by cis-regulatory evolution.

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KEGG as a reference resource for gene and protein annotation

Cited by 5,744 publications

References 14 publications

Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease

Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease

Developing reduced SNP assays from whole‐genome sequence data to estimate introgression in an organism with complex genetic patterns, the Iberian honeybee (Apis mellifera iberiensis)

Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore

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