TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: It is common in public health and epidemiology that the outcome of interest is counts of events occurrence. Analysing these data using classical linear models is mostly inappropriate, even after transformation of outcome variables due to overdispersion. Zero-adjusted mixture count models such as zero-inflated and hurdle count models are applied to count data when over-dispersion and excess zeros exist. Main objective of the current paper is to apply such models to analyse risk factors associated with human helminths (S. haematobium) particularly in a case where there's a high proportion of zero counts.", 'The data were collected during a community-based randomised control trial assessing the impact of mass drug administration (MDA) with praziquantel in Malawi, and a school-based cross sectional epidemiology survey in Zambia. Count data models including traditional (Poisson and negative binomial) models, zero modified models (zero inflated Poisson and zero inflated negative binomial) and hurdle models (Poisson logit hurdle and negative binomial logit hurdle) were fitted and compared.', 'Using Akaike information criteria (AIC), the negative binomial logit hurdle (NBLH) and zero inflated negative binomial (ZINB) showed best performance in both datasets. With regards to zero count capturing, these models performed better than other models.\Question: Do zero adjusted models with applications to analysing helminths count data?

SOLUTION: This paper showed that zero modified NBLH and ZINB models are more appropriate methods for the analysis of data with excess zeros. The choice between the hurdle and zero-inflated models should be based on the aim and endpoints of the study.

PROBLEM: Context: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms.', 'Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing.', 'The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors.', 'Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts ( P < .001). Within the isoform-specific regions of the autoantigens, 92% and 88% encoded MHC class I and class II-restricted T-cell antigen epitopes, respectively, and 70% encoded antibody binding domains. Furthermore, 80% of the autoantigen transcripts underwent noncanonical alternative splicing, which is also significantly higher than the less than 1% rate in randomly selected gene transcripts ( P < .001).\Question: Does increased noncanonical splicing of autoantigen transcripts provide the structural basis for expression of untolerized epitopes?

SOLUTION: These studies suggest that noncanonical alternative splicing may be an important mechanism for the generation of untolerized epitopes that may lead to autoimmunity. Furthermore, the product of a transcript that does not undergo alternative splicing is unlikely to be a target antigen in autoimmunity.

PROBLEM: Context: Genetic variants in DLG5, which encodes a scaffolding protein on chromosome 10q23, and tumor necrosis factor (TNF)-alpha, encoding a proinflammatory cytokine on chromosome 6p, have recently been reported to be associated with inflammatory bowel disease (IBD). We studied these variants to seek evidence of association with IBD in a large independent dataset.', "We genotyped 1104 unrelated white IBD subjects-496 with Crohn's disease, 512 with ulcerative colitis, and 96 with indeterminate colitis from the Cambridge/Eastern (UK) panel-and 760 healthy control subjects for DLG5_113G/A, DLG5_4136C/A, TNF-857C/T, and TNF-1031T/C polymorphisms. Known Crohn's disease-predisposing variants in CARD15/NOD2 were also genotyped to permit analysis for reported epistatic interactions.", ": TNF-857 was shown to be associated with IBD overall (P = 0.0079). A formal interaction test showed that TNF-857 is associated equally with ulcerative colitis and Crohn's disease. Neither of the DLG5 alleles, however, was associated with IBD (P = 0.32 and 0.35). Subgroup analysis also failed to show evidence of association between either DLG5 allele or genotype frequencies and ulcerative colitis or Crohn's disease. Stratification of TNF-alpha and DLG5 cases by CARD15 genotype made no significant difference in the strength of associations.\Question: Are genetic variants in TNF-alpha but not DLG5 associated with inflammatory bowel disease in a large United Kingdom cohort?

SOLUTION:
We have confirmed an association between the TNF-857 promoter polymorphism and IBD in a large independent UK dataset but were unable to replicate an association at the previously reported loci within DLG5. This may reflect heterogeneity between the populations, a smaller effect size than originally predicted, or possibly a false-positive result in the original study. Further fine mapping studies of the TNF promoter region and studies assessing functional consequences of TNF promoter polymorphisms are now required in IBD.