Regression Modelling of HLA Haplotype Sharing in Affected Siblings

Abstract Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer (DTC) genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows-Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale datasets with millions of samples. Furthermore we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for non-commercial use in the code repository https://github.com/23andMe/phasedibd.

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Machine learning versus regression modelling in predicting individual healthcare costs from a representative sample of the nationwide claims database in France

The European Journal of Health Economics ◽

10.1007/s10198-021-01363-4 ◽

2021 ◽

Author(s):

Alexandre Vimont ◽

Henri Leleu ◽

Isabelle Durand-Zaleski

Keyword(s):

Machine Learning ◽

Representative Sample ◽

Healthcare Costs ◽

Claims Database ◽

Regression Modelling ◽

Individual Healthcare

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Proportion and risk factors for death by euthanasia in dogs in the UK

Scientific Reports ◽

10.1038/s41598-021-88342-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Camilla Pegram ◽

Carol Gray ◽

Rowena M. A. Packer ◽

Ysabelle Richards ◽

David B. Church ◽

...

Keyword(s):

Risk Factors ◽

Poor Quality ◽

Clinical Factors ◽

Sampling Frame ◽

Additional Risk ◽

Factors Associated ◽

Regression Modelling ◽

The Uk ◽

Logistic Regression Modelling

AbstractThe loss of a pet can be particularly distressing for owners, whether the method of death is euthanasia or is unassisted. Using primary-care clinical data, this study aimed to report the demographic and clinical factors associated with euthanasia, relative to unassisted death, in dogs. Method of death (euthanasia or unassisted) and clinical cause of death were extracted from a random sample of 29,865 dogs within the VetCompass Programme from a sampling frame of 905,544 dogs under UK veterinary care in 2016. Multivariable logistic regression modelling was used to evaluate associations between risk factors and method of death. Of the confirmed deaths, 26,676 (89.3%) were euthanased and 2,487 (8.3%) died unassisted. After accounting for confounding factors, 6 grouped-level disorders had higher odds in euthanased dogs (than dogs that died unassisted), using neoplasia as the baseline. The disorders with greatest odds included: poor quality of life (OR 16.28), undesirable behaviour (OR 11.36) and spinal cord disorder (OR 6.00). Breed, larger bodyweight and increasing age were additional risk factors for euthanasia. The results highlight that a large majority of owners will face euthanasia decisions and these findings can support veterinarians and owners to better prepare for such an eventuality.

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Prevalence of intestinal schistosomiasis in pre-school aged children: a pilot survey in Marolambo District, Madagascar

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00871-y ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Caitlin Sheehy ◽

Heather Lawson ◽

Emmanuel H. Andriamasy ◽

Hannah J. Russell ◽

Alice Reid ◽

...

Keyword(s):

Epidemiological Survey ◽

Control Programme ◽

School Aged Children ◽

Regression Modelling ◽

Intestinal Schistosomiasis ◽

The Relationship ◽

Technical Guidance ◽

National Control ◽

Soil Transmitted Helminthiasis ◽

National Control Programme

AbstractSchool-aged children (SAC) have a considerable burden of intestinal schistosomiasis in Madagascar yet its burden in pre-school aged children (PSAC) is currently overlooked. To assess the at-risk status of PSAC, we undertook a pilot epidemiological survey in June 2019 examining children (n = 89), aged 2–4-years of balanced gender, in six remote villages in Marolambo District, Madagascar. Diagnosis included use of urine-circulating cathodic antigen (CCA) dipsticks and coproscopy of stool with duplicate Kato-Katz (K-K) thick smears. Prevalence of intestinal schistosomiasis by urine-CCA was 67.4% (95% confidence interval [CI]: 56.5–77.2%) and 35.0% (95% CI: 24.7–46.5%) by K-K. The relationship between faecal eggs per gram (epg) and urine-CCA G-scores (G1 to G10) was assessed by linear regression modelling, finding for every increment in G-score, epg increased by 20.4 (6.50–34.4, P = 0.006). Observed proportions of faecal epg intensities were light (78.6%), moderate (17.9%) and heavy (3.6%). Soil-transmitted helminthiasis was noted, prevalence of ascariasis was 18.8% and trichuriasis was 33.8% (hookworm was not reported). Co-infection of intestinal schistosomiasis and soil-transmitted helminthiasis occurred in 36.3% of PSAC. These results provide solid evidence highlighting the overlooked burden of intestinal schistosomiasis in PSAC, and they also offer technical guidance for better surveillance data for the Madagascan national control programme.

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