A comparison of genomic copy number calls by Partek Genomics Suite, Genotyping Console and Birdsuite algorithms to quantitative PCR

<p>Abstract</p> <p>Background</p> <p>Copy number variants are >1 kb genomic amplifications or deletions that can be identified using array platforms. However, arrays produce substantial background noise that contributes to high false discovery rates of variants. We hypothesized that quantitative PCR could finitely determine copy number and assess the validity of calling algorithms.</p> <p>Results</p> <p>Using data from 29 Affymetrix SNP 6.0 arrays, we determined copy numbers using three programs: Partek Genomics Suite, Affymetrix Genotyping Console 2.0 and Birdsuite. We compared array calls at 25 chromosomal regions to those determined by qPCR and found nearly identical calls in regions of copy number 2. Conversely, agreement differed in regions called variant by at least one method. The highest overall agreement in calls, 91%, was between Birdsuite and quantitative PCR. Partek Genomics Suite calls agreed with quantitative PCR 76% of the time while the agreement of Affymetrix Genotyping Console 2.0 with quantitative PCR was 79%.</p> <p>Conclusions</p> <p>In 38 independent samples, 96% of Birdsuite calls agreed with quantitative PCR. Analysis of three copy number calling programs and quantitative PCR showed Birdsuite to have the greatest agreement with quantitative PCR.</p

Experimental measurement of specific impulse distribution and transient deformation of plates subjected to near-field explosive blasts

The shock wave generated from a high explosive detonation can cause significant damage to any objects that it encounters, particularly those objects located close to the source of the explosion. Understanding blast wave development and accurately quantifying its effect on structural systems remains a considerable challenge to the scientific community. This paper presents a comprehensive experimental study into the loading acting on, and subsequent deformation of, targets subjected to near-field explosive detonations. Two experimental test series were conducted at the University of Sheffield (UoS), UK, and the University of Cape Town (UCT), South Africa, where blast load distributions using Hopkinson pressure bars and dynamic target deflections using digital image correlation were measured respectively. It is shown through conservation of momentum and Hopkinson-Cranz scaling that initial plate velocity profiles are directly proportional to the imparted impulse distribution, and that spatial variations in loading as a result of surface instabilities in the expanding detonation product cloud are significant enough to influence the transient displacement profile of a blast loaded plate

Genome-Wide Analysis of Copy Number Variation in Type 1 Diabetes

Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Increasing vegetable intakes: rationale and systematic review of published interventions

Purpose While the health benefits of a high fruit and vegetable consumption are well known and considerable work has attempted to improve intakes, increasing evidence also recognises a distinction between fruit and vegetables, both in their impacts on health and in consumption patterns. Increasing work suggests health benefits from a high consumption specifically of vegetables, yet intakes remain low, and barriers to increasing intakes are prevalent making intervention difficult. A systematic review was undertaken to identify from the published literature all studies reporting an intervention to increase intakes of vegetables as a distinct food group. Methods Databases—PubMed, PsychInfo and Medline—were searched over all years of records until April 2015 using pre-specified terms. Results Our searches identified 77 studies, detailing 140 interventions, of which 133 (81 %) interventions were conducted in children. Interventions aimed to use or change hedonic factors, such as taste, liking and familiarity (n = 72), use or change environmental factors (n = 39), use or change cognitive factors (n = 19), or a combination of strategies (n = 10). Increased vegetable acceptance, selection and/or consumption were reported to some degree in 116 (83 %) interventions, but the majority of effects seem small and inconsistent. Conclusions Greater percent success is currently found from environmental, educational and multi-component interventions, but publication bias is likely, and long-term effects and cost-effectiveness are rarely considered. A focus on long-term benefits and sustained behaviour change is required. Certain population groups are also noticeably absent from the current list of tried interventions

Genetically predicted circulating B vitamins in relation to digestive system cancers

Funder: United Kingdom Research and Innovation Future Leaders Fellowship (MR/T043202/1)Funder: EC‐Innovative Medicines Initiative (BigData@Heart)Funder: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z)Abstract: Background: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer