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A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

Overview of attention for article published in Respiratory Research, June 2018
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Title
A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research
Published in
Respiratory Research, June 2018
DOI 10.1186/s12931-018-0795-y
Pubmed ID
Authors

Sangeetha Vishweswaraiah, Leema George, Natarajan Purushothaman, Koustav Ganguly

Abstract

Early life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function determining genes using microarray analysis (GSE80078). Advancement of high-throughput techniques like deep sequencing (eg. RNA-seq) and microarray have resulted in an explosion of genomic data in the online public repositories which however remains under-exploited. Strategic curation of publicly available genomic data with a mouse-human translational approach can effectively implement "3R- Tenet" by reducing screening experiments with animals and performing mechanistic studies using physiologically relevant in vitro model systems. Therefore, we sought to analyze the association of functional variations within human orthologs of mouse lung function candidate genes in a publicly available COPD lung RNA-seq data-set. Association of missense single nucleotide polymorphisms, insertions, deletions, and splice junction variants were analyzed for susceptibility to COPD using RNA-seq data of a Korean population (GSE57148). Expression of the associated genes were studied using the Gene Paint (mouse embryo) and Human Protein Atlas (normal adult human lung) databases. The genes were also assessed for replication of the associations and expression in COPD-/mouse cigarette smoke exposed lung tissues using other datasets. Significant association (p <  0.05) of variations in 20 genes to higher COPD susceptibility have been detected within the investigated cohort. Association of HJURP, MCRS1 and TLR8 are novel in relation to COPD. The associated ADAM19 and KIT loci have been reported earlier. The remaining 15 genes have also been previously associated to COPD. Differential transcript expression levels of the associated genes in COPD- and/ or mouse emphysematous lung tissues have been detected. Our findings suggest strategic mouse-human datamining approaches can identify novel COPD candidate genes using existing datasets in the online repositories. The candidates can be further evaluated for mechanistic role through in vitro studies using appropriate primary cells/cell lines. Functional studies can be limited to transgenic animal models of only well supported candidate genes. This approach will lead to a significant reduction of animal experimentation in respiratory research.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 29%
Unspecified 4 24%
Student > Master 2 12%
Student > Bachelor 2 12%
Student > Ph. D. Student 1 6%
Other 3 18%
Readers by discipline Count As %
Unspecified 6 35%
Biochemistry, Genetics and Molecular Biology 4 24%
Computer Science 3 18%
Agricultural and Biological Sciences 1 6%
Immunology and Microbiology 1 6%
Other 2 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 June 2018.
All research outputs
#9,975,547
of 13,044,924 outputs
Outputs from Respiratory Research
#1,280
of 1,543 outputs
Outputs of similar age
#187,240
of 270,638 outputs
Outputs of similar age from Respiratory Research
#20
of 23 outputs
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