Biology subjects

Collins, C.

Publications and source records attributed to Collins, C..

5 recordsLinked to original sources

bioRxiv2018

The impact of a reduced calorie, macronutrient diet change on Caucasian males in relation to genotypes associated with obesity, increased BMI and dietary response.

Obesity is a growing crisis within the 1st world and the causes of obesity are well studied: a lack of physical activity combined with an increased calorie intake. This energy imbalance leads to fat accumulation leading to eventual obesity. Whilst the cause may appear clear, the options of lifestyle change and/or diet planning that is efficient with effective sustainability has been harder to come by. Genetic variants linked to obesity may hold clues on how to best customise a diet plan to an individual leading to an easier to change lifestyle with better sustainability. This study aimed to find correlations with a diet change that decreased kcal intake by 200kcal per day with a macronutrient alteration (decreased carbohydrates and increased unsaturated fat) and genetic components to discover responders and non-responders. Within the study group of Caucasian males the genes TCF7L2, TFAP2B, PPARG2 and FTO all impacted the response of the dietary intervention. In conclusion it would be prudent to consider DNA analysis as part of a battery of diet and lifestyle tests to personalise a sustainable and effective lifestyle/dietary intervention to help control weight.

genomics↗

bioRxiv2018

MechRNA: prediction of lncRNA mechanisms from RNA-RNA and RNA-protein interactions

MotivationLong non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides that do not get translated into proteins. Often these transcripts are processed (spliced, capped, polyadenylated) and some are known to have important biological functions. However, most lncRNAs have unknown or poorly understood functions. Nevertheless, because of their potential role in cancer, lncRNAs are receiving a lot of attention, and the need for computational tools to predict their possible mechanisms of action is more than ever. Fundamentally, most of the known lncRNA mechanisms involve RNA-RNA and/or RNA-protein interactions. Through accurate predictions of each kind of interaction and integration of these predictions, it is possible to elucidate potential mechanisms for a given lncRNA.\n\nApproachHere we introduce MechRNA, a pipeline for corroborating RNA-RNA interaction prediction and protein binding prediction for identifying possible lncRNA mechanisms involving specific targets or on a transcriptome-wide scale. The first stage uses a version of IntaRNA2 with added functionality for efficient prediction of RNA-RNA interactions with very long input sequences, allowing for large-scale analysis of lncRNA interactions with little or no loss of optimality. The second stage integrates protein binding information pre-computed by GraphProt, for both the lncRNA and the target. The final stage involves inferring the most likely mechanism for each lncRNA/target pair. This is achieved by generating candidate mechanisms from the predicted interactions, the relative locations of these interactions and correlation data, followed by selection of the most likely mechanistic explanation using a combined p-value.\n\nResultsWe applied MechRNA on a number of recently identified cancer-related lncRNAs (PCAT1, PCAT29, ARLnc1) and also on two well-studied lncRNAs (PCA3 and 7SL). This led to the identification of hundreds of high confidence potential targets for each lncRNA and corresponding mechanisms. These predictions include the known competitive mechanism of 7SL with HuR for binding on the tumor suppressor TP53, as well as mechanisms expanding what is known about PCAT1 and ARLn1 and their targets BRCA2 and AR, respectively. For PCAT1-BRCA2, the mechanism involves competitive binding with HuR, which we confirmed using HuR immunoprecipitation assays.\n\nAvailabilityMechRNA is available for download at https://bitbucket.org/compbio/mechrna\n\nContactbackofen@informatik.uni-freiburg.de, cenksahi@indiana.edu\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2017

Stimulation of the final cell cycle in the stomatal lineage by the cyclin CYCD7;1 under regulation of the MYB transcription factor FOUR-LIPS

Abstract (180 words)Stomatal guard cells are formed through a sequence of asymmetric and symmetric divisions in the epidermis of the sporophyte of most land plants. We show that several D-type cyclins are consecutively activated in the stomatal linage in the epidermis of Arabidopsis thaliana. Whereas CYCD2;1 and CYCD3;2 are activated in the meristemoids early in the lineage, CYCD7;1 is activated before the final division. CYCD7;1 expression peaks in the guard mother cell, where its transcription is modulated by the FOUR-LIPS/MYB88 transcription factor. FOUR-LIPS/MYB88 interacts with the CYCD7;1 promoter and represses CYCD7;1 transcription. CYCD7;1 stimulates the final symmetric division in the stomatal lineage, since guard cell formation is delayed in the cycd7;1 mutant epidermis and guard mother cell (GMC) divisions in four-lips mutant guard mother cells are limited by loss of function of CYCD7;1. Hence, the precise activation of a specific D-type cyclin, CYCD7;1, is required for correct timing of the last symmetric division that creates the stomatal guards cells, and CYCD7;1 expression is regulated by the FLP/MYB pathway that ensures cell cycle arrest in the stomatal guard cells.\n\nSummary StatementThe formation of paired guard cells in the epidermis of the Arabidopsis thaliana shoot, requires the activity of the D-type cyclin CYCD7;1 for the normal timing of the final division.

plant biology↗

bioRxiv2017

A Phylogenetic Method To Perform Genome-Wide Association Studies In Microbes That Accounts For Population Structure And Recombination

Genome-Wide Association Studies (GWAS) in microbial organisms have the potential to vastly improve the way we understand, manage, and treat infectious diseases. Yet, GWAS methods established thus far remain insufficiently able to capitalise on the growing wealth of bacterial and viral genetic sequence data. Facing clonal population structure and homologous recombination, existing GWAS methods struggle to achieve both the precision necessary to reject spurious findings and the power required to detect associations in microbes. In this paper, we introduce a novel phylogenetic approach that has been tailor-made for microbial GWAS, which is applicable to organisms ranging from purely clonal to frequently recombining, and to both binary and continuous phenotypes. Our approach is robust to the confounding effects of both population structure and recombination, while maintaining high statistical power to detect associations. Thorough testing via application to simulated data provides strong support for the power and specificity of our approach and demonstrates the advantages offered over alternative cluster-based and dimension-reduction methods. Two applications to Neisseria meningitidis illustrate the versatility and potential of our method, confirming previously-identified penicillin resistance loci and resulting in the identification of both well-characterised and novel drivers of invasive disease. Our method is implemented as an open-source R package called treeWAS which is freely available at https://github.com/caitiecollins/treeWAS.

microbiology↗

bioRxiv2017

Environmental Conditions And Agronomic Practices Induce Consistent Global Changes In DNA Methylation Patterns In Grapevine (Vitis vinifera cv Shiraz)

Fruit attributes that affect wine quality are thought to be largely driven by the interaction of grapevines genetic characteristics with environmental factors (i.e. climate, soil and topography) and vineyard management. All these variables, in conjunction with the wine making process, give a wine its distinctive character. Understanding how grapevines perceive and adapt to a changing environment will provide us with an insight into how to better manage crop quality. Mounting evidence suggests that epigenetic mechanisms are a key interface between the environment and the genotype that ultimately affect the plants phenotype. Moreover, it is now widely accepted that epigenetic mechanisms are a source of useful variability during crop varietal selection that could affect crop performance. While the contribution of DNA methylation to plant performance has been extensively studied in other major crops, very little work has been done in grapevine. Here we used Methylation Sensitive Amplified Polymorphisms to obtain global patterns of DNA methylation, and to identify the main drivers of epigenetic diversity across 22 vineyards planted with the cultivar Shiraz in six distinctive wine areas of a major wine zone, The Barossa, South Australia. The observed epigenetic profiles showed a high level of differentiation that grouped vineyards by their area of provenance despite the low genetic differentiation between vineyards and sub-regions. Furthermore, pairwise epigenetic distances between vineyards with similar management systems showed a significant correlation with geographic distance. Finally, methylation sensitive Genotyping By Sequencing identified 3,598 differentially methylated genes that were assigned to 1,144 unique GO terms of which 8.6% were associated with response to environmental stimulus. Taken together, our results indicate that the intensity and directionality of DNA methylation differentiation between vineyards and wine sub-regions within The Barossa are driven by management and local growing conditions. Finally, we discuss how epigenetic variability can be used as a tool to understand and potentially modulate terroir in grapevine.

plant biology↗