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- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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- Smith, Bradley P., et al.
(författare)
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Taxonomic status of the Australian dingo : the case for Canis dingo Meyer, 1793
- 2019
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Ingår i: Zootaxa. - : MAGNOLIA PRESS. - 1175-5326 .- 1175-5334. ; 4564:1, s. 173-197
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Tidskriftsartikel (refereegranskat)abstract
- The taxonomic status and systematic nomenclature of the Australian dingo remain contentious, resulting in decades of inconsistent applications in the scientific literature and in policy. Prompted by a recent publication calling for dingoes to be considered taxonomically as domestic dogs (Jackson et al. 2017, Zootaxa 4317, 201-224), we review the issues of the taxonomy applied to canids, and summarise the main differences between dingoes and other canids. We conclude that (1) the Australian dingo is a geographically isolated (allopatric) species from all other Canis, and is genetically, phenotypically, ecologically, and behaviourally distinct; and (2) the dingo appears largely devoid of many of the signs of domestication, including surviving largely as a wild animal in Australia for millennia. The case of defining dingo taxonomy provides a quintessential example of the disagreements between species concepts (e.g., biological, phylogenetic, ecological, morphological). Applying the biological species concept sensu stricto to the dingo as suggested by Jackson et al. (2017) and consistently across the Canidae would lead to an aggregation of all Canis populations, implying for example that dogs and wolves are the same species. Such an aggregation would have substantial implications for taxonomic clarity, biological research, and wildlife conservation. Any changes to the current nomen of the dingo (currently Canis dingo Meyer, 1793), must therefore offer a strong, evidence-based argument in favour of it being recognised as a subspecies of Canis lupus Linnaeus, 1758, or as Canis familiaris Linnaeus, 1758, and a successful application to the International Commission for Zoological Nomenclature - neither of which can be adequately supported. Although there are many species concepts, the sum of the evidence presented in this paper affirms the classification of the dingo as a distinct taxon, namely Canis dingo.
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- Ventham, N. T., et al.
(författare)
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Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
- 2016
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8(+) T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.
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