scholarly journals Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Fiona Allum ◽  
◽  
Xiaojian Shao ◽  
Frédéric Guénard ◽  
Marie-Michelle Simon ◽  
...  

Abstract Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

1997 ◽  
Vol 36 (8-9) ◽  
pp. 307-311 ◽  
Author(s):  
R. Y. G. Andoh ◽  
C. Declerck

Rapid urbanisation and its consequent increase in impermeable surface areas and changes in land use has generally resulted in problems of flooding and heavy pollution of urban streams and other receiving waters. This has often been coupled with ground water depletion and a threat to water resources. The first part of this paper presents an alternative drainage philosophy and strategy which mimics nature's way by slowing down (attenuating) the movement of urban runoff. This approach results in cost-effective, affordable and sustainable drainage schemes. The alternative strategy can be described as one of prevention rather than cure by effecting controls closer to source rather than the traditional approach which results in the transfer of problems downstream, resulting in its cumulation and the need for large scale, centralised control. The second part describes a research project which has been launched in order to quantify the cost and operational benefits of source control and distributed storage. Details of the methodology of the modelling and simulation processes which are being followed to achieve this target are presented.


Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 536 ◽  
Author(s):  
Xiaobo Zhao ◽  
Liming Gan ◽  
Caixia Yan ◽  
Chunjuan Li ◽  
Quanxi Sun ◽  
...  

Long non-coding RNAs (lncRNAs) are involved in various regulatory processes although they do not encode protein. Presently, there is little information regarding the identification of lncRNAs in peanut (Arachis hypogaea Linn.). In this study, 50,873 lncRNAs of peanut were identified from large-scale published RNA sequencing data that belonged to 124 samples involving 15 different tissues. The average lengths of lncRNA and mRNA were 4335 bp and 954 bp, respectively. Compared to the mRNAs, the lncRNAs were shorter, with fewer exons and lower expression levels. The 4713 co-expression lncRNAs (expressed in all samples) were used to construct co-expression networks by using the weighted correlation network analysis (WGCNA). LncRNAs correlating with the growth and development of different peanut tissues were obtained, and target genes for 386 hub lncRNAs of all lncRNAs co-expressions were predicted. Taken together, these findings can provide a comprehensive identification of lncRNAs in peanut.


2019 ◽  
Vol 21 (2) ◽  
pp. 198-204 ◽  
Author(s):  
Kaiyu Xie ◽  
Ali Reza Kamali

Molten salt electrolytic reduction of Fe2O3 in the presence of water is proposed as a sustainable and cost-effective approach for large-scale production of iron.


2013 ◽  
Vol 14 (1) ◽  
pp. 135-141 ◽  
Author(s):  
C. Santos ◽  
C. Matos ◽  
F. Taveira-Pinto

Greywater (GW) can be an important resource for urban water consumption, replacing potable water for purposes that do not require drinking water quality. If applied on a large scale, this practice will reduce the potable water demand and the wastewater produced in urban areas, minimizing the negative impacts and costs of water extraction and wastewater treatment. A correct characterization of GW is important to assess its potential for a direct reuse or, if not possible, to make a correct definition of a feasible and cost-effective treatment system. This article aims to contribute to the characterization of GW produced in washbasins and showers in domestic and public buildings. A compilation of several works on GW collection and sampling produced by the authors is presented. Samples were taken from GW produced in showers and washbasins in households, changing rooms and in a restaurant. Results are compared with values presented in similar studies and compared with standards and guidelines published in different countries.


2018 ◽  
Author(s):  
Adrià Fernández-Torras ◽  
Miquel Duran-Frigola ◽  
Patrick Aloy

AbstractBackgroundThe integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations and point to new therapeutic biomarkers. However, the inherent complexity of transcriptional signatures, with thousands of differentially expressed genes, makes them hard to interpret, thus giving poor mechanistic insights and hampering translation to clinics.MethodsTo simplify drug signatures, we have developed a network-based methodology to identify functionally coherent gene modules. Our strategy starts with the calculation of drug-gene correlations and is followed by a pathway-oriented filtering and a network-diffusion analysis across the interactome.ResultsWe apply our approach to 189 drugs tested in 671 cancer cell lines and observe a connection between gene expression levels of the modules and mechanisms of action of the drugs. Further, we characterize multiple aspects of the modules, including their functional categories, tissue-specificity and prevalence in clinics. Finally, we prove the predictive capability of the modules and demonstrate how they can be used as gene sets in conventional enrichment analyses.ConclusionsNetwork biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened.


Environmental science and management is often the most discussed subject nowadays all over the world. In a number of countries, presently plenty of harms are associated with the effluent by industrial due to growing industrialization; this issue should be considered at large scale. Textile sector is one of the leading areas, which uses a high amount of chemicals and creating environmental pollution. Textile wet processing sector uses a lot of chemicals, surfactants and synthetic dyes, hence produce a large amount of wastewater having a high concentration of chemicals. This research is an effort to investigate the amount of residue remained in liquor after bleaching and reuses this liquor by adding a few chemicals according to the requirement. Afterward, the comparison was made between the bleached sample with fresh liquor and bleached sample with reused liquor. It was observed that bleaching with reused liquor shows good results though these results are insignificantly less than fresh bleaching liquor. On the other hand, fortunately, the color yield of dyed fabric bleached with reused liquor is higher than fresh liquor.


2019 ◽  
Author(s):  
Meng Lin ◽  
Christian Caberto ◽  
Peggy Wan ◽  
Yuqing Li ◽  
Annette Lum-Jones ◽  
...  

AbstractStatistical imputation applied to genome-wide array data is the most cost-effective approach to complete the catalog of genetic variation in a study population. However, imputed genotypes in underrepresented populations incur greater inaccuracies due to ascertainment bias and a lack of representation among reference individuals,, further contributing to the obstacles to study these populations. Here we examined the consequences due to the lack of representation by genotyping a functionally important, Polynesian-specific variant, rs373863828, in the CREBRF gene, in a large number of self-reported Native Hawai’ians (N=3,693) from the Multiethnic Cohort. We found the derived allele of rs373863828 was significantly associated with several adiposity traits with large effects (e.g. 0.214 s.d., or approximately 1.28 kg/m2, per allele, in BMI as the most significant; P = 7.5×10−5). Due to the current absence of Polynesian representation in publicly accessible reference sequences, rs373863828 or any of its proxies could not be tested through imputation using these existing resources. Moreover, the association signals at this Polynesian-specific variant could not be captured by alternative approaches, such as admixture mapping. In contrast, highly accurate imputation can be achieved even if a small number (<200) of Polynesian reference individuals were available. By constructing an internal set of Polynesian reference individuals, we were able to increase sample size for analysis up to 3,936 individuals, and improved the statistical evidence of association (e.g. p = 1.5×10−7, 3×10−6, and 1.4×10−4 for BMI, hip circumference, and T2D, respectively). Taken together, our results suggest the alarming possibility that lack of representation in reference panels would inhibit discovery of functionally important, population-specific loci such as CREBRF. Yet, they could be easily detected and prioritized with improved representation of diverse populations in sequencing studies.


2017 ◽  
Author(s):  
Raamesh Deshpande ◽  
Justin Nelson ◽  
Scott W. Simpkins ◽  
Michael Costanzo ◽  
Jeff S. Piotrowski ◽  
...  

Large-scale genetic interaction screening is a powerful approach for unbiased characterization of gene function and understanding systems-level cellular organization. While genome-wide screens are desirable as they provide the most comprehensive interaction profiles, they are resource and time-intensive and sometimes infeasible, depending on the species and experimental platform. For these scenarios, optimal methods for more efficient screening while still producing the maximal amount of information from the resulting profiles are of interest.To address this problem, we developed an optimal algorithm, called COMPRESS-GI, which selects a small but informative set of genes that captures most of the functional information contained within genome-wide genetic interaction profiles. The utility of this algorithm is demonstrated through an application of the approach to define a diagnostic mutant set for large-scale chemical genetic screens, where more than 13,000 compound screens were achieved through the increased throughput enabled by the approach. COMPRESS-GI can be broadly applied for directing genetic interaction screens in other contexts, including in species with little or no prior genetic-interaction data.


2020 ◽  
Vol 29 (13) ◽  
pp. 2275-2284
Author(s):  
Meng Lin ◽  
Christian Caberto ◽  
Peggy Wan ◽  
Yuqing Li ◽  
Annette Lum-Jones ◽  
...  

Abstract Statistical imputation applied to genome-wide array data is the most cost-effective approach to complete the catalog of genetic variation in a study population. However, imputed genotypes in underrepresented populations incur greater inaccuracies due to ascertainment bias and a lack of representation among reference individuals, further contributing to the obstacles to study these populations. Here we examined the consequences due to the lack of representation by genotyping in a large number of self-reported Native Hawaiians (N = 3693) a functionally important, Polynesian-specific variant in the CREBRF gene, rs373863828. We found the derived allele was significantly associated with several adiposity traits with large effects (e.g. ~ 1.28 kg/m2 per allele in body mass index as the most significant; P = 7.5 × 10−5), consistent with the original findings in Samoans. Due to the current absence of Polynesian representation in publicly accessible reference sequences, rs373863828 or its proxies could not be tested through imputation using these existing resources. Moreover, the association signals at the entire CREBRF locus could not be captured by alternative approaches, such as admixture mapping. In contrast, highly accurate imputation can be achieved even if a small number (&lt;200) of internally constructed Polynesian reference individuals were available; this would increase sample size and improve the statistical evidence of associations. Taken together, our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci such as CREBRF. Yet, they could be easily detected and prioritized with improved representation of diverse populations in sequencing studies.


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