Mammals have a large cohort of endo- and ecto- symbiotic microorganisms (the microbiome) that potentially influence host phenotypes. There have been numerous exploratory studies of these symbiotic organisms in humans and other animals, often with the aim of relating the microbiome to a complex phenotype such as body mass index (BMI) or disease state. Here, we describe an efficient methodology for predicting complex traits from quantitative microbiome profiles. The method was demonstrated by predicting inflammatory bowel disease (IBD) status and BMI from human microbiome data, and enteric greenhouse gas production from dairy cattle rumen microbiome profiles. The method uses unassembled massively parallel sequencing (MPS) data to form metagenomic relationship matrices (analogous to genomic relationship matrices used in genomic predictions) to predict IBD, BMI and methane production phenotypes with useful accuracies (r = 0.423, 0.422 and 0.466 respectively). Our results show that microbiome profiles derived from MPS can be used to predict complex phenotypes of the host. Although the number of biological replicates used here limits the accuracy that can be achieved, preliminary results suggest this approach may surpass current prediction accuracies that are based on the host genome. This is especially likely for traits that are largely influenced by the gut microbiota, for example digestive tract disorders or metabolic functions such as enteric methane production in cattle.
BackgroundVariation of microorganism communities in the rumen of cattle (Bos taurus) is of great interest because of possible links to economically or environmentally important traits, such as feed conversion efficiency or methane emission levels. The resolution of studies investigating this variation may be improved by utilizing untargeted massively parallel sequencing (MPS), that is, sequencing without targeted amplification of genes. The objective of this study was to develop a method which used MPS to generate “rumen metagenome profiles”, and to investigate if these profiles were repeatable among samples taken from the same cow. Given faecal samples are much easier to obtain than rumen fluid samples; we also investigated whether rumen metagenome profiles were predictive of faecal metagenome profiles.ResultsRather than focusing on individual organisms within the rumen, our method used MPS data to generate quantitative rumen micro-biome profiles, regardless of taxonomic classifications. The method requires a previously assembled reference metagenome. A number of such reference metagenomes were considered, including two rumen derived metagenomes, a human faecal microflora metagenome and a reference metagenome made up of publically available prokaryote sequences. Sequence reads from each test sample were aligned to these references. The “rumen metagenome profile” was generated from the number of the reads that aligned to each contig in the database. We used this method to test the hypothesis that rumen fluid microbial community profiles vary more between cows than within multiple samples from the same cow. Rumen fluid samples were taken from three cows, at three locations within the rumen. DNA from the samples was sequenced on the Illumina GAIIx. When the reads were aligned to a rumen metagenome reference, the rumen metagenome profiles were repeatable (P < 0.00001) by cow regardless of location of sampling rumen fluid. The repeatability was estimated at 9%, albeit with a high standard error, reflecting the small number of animals in the study. Finally, we compared rumen microbial profiles to faecal microbial profiles. Our hypothesis, that there would be a stronger correlation between faeces and rumen fluid from the same cow than between faeces and rumen fluid from different cows, was not supported by our data (with much greater significance of rumen versus faeces effect than animal effect in mixed linear model).ConclusionsWe have presented a simple and high throughput method of metagenome profiling to assess the similarity of whole metagenomes, and illustrated its use on two novel datasets. This method utilises widely used freeware. The method should be useful in the exploration and comparison of metagenomes.
Dietary changes can be helpful in preventing or treating a variety of prevalent health problems. Physicians can be helpful in helping patients make positive dietary changes, be physically active and lose weight, but, for a variety of reasons, many physicians do little nutrition counseling. There is a need for brief, user-friendly tools to enable physicians to rapidly and accurately assess patients' diets and exercise habits as well as provide information to aid the physician in delivering effective nutrition counseling. The purpose of this paper is to discuss two new tools, WAVE and REAP, that have been developed by the Nutrition Academic Award to help physicians and other health care providers conduct nutrition assessment and counseling with their patients in a practical and effective manner. The WAVE acronym and tool is designed to encourage provider/patient dialogue about the pros and cons of the patients' current status related to Weight, Activity, Variety and Excess. The Rapid Eating and Activity Assessment for Patients (REAP) is a brief validated questionnaire that is designed to aid providers in performing a brief assessment of diet and physical activity. An accompanying Physician Key aids the provider in discussing the patient's answers and counseling them appropriately. REAP and WAVE can be helpful tools to facilitate nutrition assessment and counseling in the provider office. Depending on patients' health priorities and how much time is available, these tools can be used in a variety of ways to discuss nutrition with patients during a clinical encounter in 1-9 min.
Key messageNon-additive genetic effects seem to play a substantial role in the expression of complex traits in sugarcane. Including non-additive effects in genomic prediction models significantly improves the prediction accuracy of clonal performance.AbstractIn the recent decade, genetic progress has been slow in sugarcane. One reason might be that non-additive genetic effects contribute substantially to complex traits. Dense marker information provides the opportunity to exploit non-additive effects in genomic prediction. In this study, a series of genomic best linear unbiased prediction (GBLUP) models that account for additive and non-additive effects were assessed to improve the accuracy of clonal prediction. The reproducible kernel Hilbert space model, which captures non-additive genetic effects, was also tested. The models were compared using 3,006 genotyped elite clones measured for cane per hectare (TCH), commercial cane sugar (CCS), and Fibre content. Three forward prediction scenarios were considered to investigate the robustness of genomic prediction. By using a pseudo-diploid parameterization, we found significant non-additive effects that accounted for almost two-thirds of the total genetic variance for TCH. Average heterozygosity also had a major impact on TCH, indicating that directional dominance may be an important source of phenotypic variation for this trait. The extended-GBLUP model improved the prediction accuracies by at least 17% for TCH, but no improvement was observed for CCS and Fibre. Our results imply that non-additive genetic variance is important for complex traits in sugarcane, although further work is required to better understand the variance component partitioning in a highly polyploid context. Genomics-based breeding will likely benefit from exploiting non-additive genetic effects, especially in designing crossing schemes. These findings can help to improve clonal prediction, enabling a more accurate identification of variety candidates for the sugarcane industry.
Sugarcane is a major industrial crop cultivated in tropical and subtropical regions of the world. It is the primary source of sugar worldwide, accounting for more than 70% of world sugar consumption. Additionally, sugarcane is emerging as a source of sustainable bioenergy. However, the increase in productivity from sugarcane has been small compared to other major crops, and the rate of genetic gains from current breeding programs tends to be plateauing. In this review, some of the main contributors for the relatively slow rates of genetic gain are discussed, including (i) breeding cycle length and (ii) low narrow-sense heritability for major commercial traits, possibly reflecting strong non-additive genetic effects involved in quantitative trait expression. A general overview of genomic selection (GS), a modern breeding tool that has been very successfully applied in animal and plant breeding, is given. This review discusses key elements of GS and its potential to significantly increase the rate of genetic gain in sugarcane, mainly by (i) reducing the breeding cycle length, (ii) increasing the prediction accuracy for clonal performance, and (iii) increasing the accuracy of breeding values for parent selection. GS approaches that can accurately capture non-additive genetic effects and potentially improve the accuracy of genomic estimated breeding values are particularly promising for the adoption of GS in sugarcane breeding. Finally, different strategies for the efficient incorporation of GS in a practical sugarcane breeding context are presented. These proposed strategies hold the potential to substantially increase the rate of genetic gain in future sugarcane breeding.
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