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- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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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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| 8. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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| 10. |
- Trak-Fellermeier, María A., et al.
(författare)
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Pearls randomized lifestyle trial in pregnant hispanic women with overweight/obesity : Gestational weight gain and offspring birthweight
- 2019
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Ingår i: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. - 1178-7007. ; 12, s. 225-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inappropriate gestational weight gain (GWG) has been associated with adverse perinatal events. High rates of GWG have been reported among Hispanic women. Observational studies indicate that dietary and physical activity interventions during the prenatal period may improve maternal and infant health, but very few randomized trials have been conducted among high-risk overweight/obese Hispanic women. Accordingly, we conducted a lifestyle intervention among high-risk pregnant women and evaluated its impact on achieving appropriate GWG and on improving birthweight. Methods: Eligible overweight/obese women presenting at the University Hospital in Puerto Rico with a singleton pregnancy before 16 gestational weeks were recruited and randomized to lifestyle intervention (n=15) or control group (n=16). The lifestyle intervention focused on improving physical activity and diet quality and optimizing caloric intake. We evaluated the impact of the lifestyle intervention on achieving appropriate GWG and on infant birthweight. Poisson and linear regression analyses were performed. Results: The primary intent to treat analysis showed no significant effect on achievement of appropriate GWG/week through 36 weeks in the intervention group (4/15 women) when compared with the control group (3/16 women) (adjusted incidence rate ratio =1.14; 95% CI: 0.20, 6.67). Although not statistically significant, women in the intervention group (6/15) were 1.7 times more likely to achieve appropriate weekly GWG until delivery when compared with controls (4/16 women) (adjusted incidence rate ratio = 1.67; 95% CI: 0.40, 6.94). We observed lower adjusted birthweight-for-length z-scores in the intervention compared with the control group among male newborns with z-score difference −1.74 (−3.04, −0.43), but not among females −0.83 (−3.85, 2.19). These analyses were adjusted for age and baseline body mass index. Conclusion: Although larger studies are required to determine whether women with obesity may benefit from prenatal lifestyle interventions targeting GWG, our results are suggestive of the intervention improving adherence to established Institute of Medicine guidelines.
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