New integrated analytical approach reveals molecules involved in disease

November 8, 2018, Osaka University
The MIGWAS pipeline integrates GWAS results, cell-type specific expression profiles of miRNAs, and in silico miRNA-gene target prediction algorithms to identify tissue specific contribution of miRNA to diseases and to detect biomarker miRNAs. Credit: Osaka University

Technological advances have enabled scientists to obtain massive amounts of data on different information-carrying molecules in cells and tissues, such as DNA, proteins and various forms of RNA. However, to date, it has been difficult to perform integrated analyses of such information to further our knowledge on the molecules and processes involved in the development of particular diseases.

Researchers from an Osaka University-led collaboration have made a major contribution to our understanding of the complex relationships among the components of cells and tissues. They have established a new analytical approach called MIGWAS that integrates information from two different sources. One of these is associations between genetic variants and diseases and other traits, while the other is data about networks formed between small regulatory molecules called miRNAs and the that they . The team showed that this in silico screening approach provides improved power to reveal novel cellular components associated with diseases and other traits, tissue-specifically.

The use of miRNA data in this way was prompted by accumulating findings on the importance of miRNAs in various physiological functions and diseases. miRNAs are small products of DNA that do not themselves encode proteins, but instead bind to mRNAs to regulate gene expression. In this latest study, the researchers employed previously obtained data on the expression of around 1,800 miRNAs in different cells. They searched for overlaps between these miRNAs and the genes they target on the one hand, and genes identified elsewhere as being linked to diseases and other traits by studies focusing directly on the genetic code on the other.

"It has been difficult to obtain convincing data about the effects of miRNAs as their short length means that they are encoded by only a very small part of the genome," lead author Saori Sakaue says. "Our MIGWAS approach linking findings from and miRNA-target networks helps to overcome this. It successfully obtained significant results for miRNA/target gene enrichment for traits such as height and type 2 diabetes across different ethnic groups."

The team attempted to validate this approach by focusing on the disease rheumatoid arthritis (RA), using data on single-nucleotide polymorphisms from nearly 20,000 RA cases and over 60,000 corresponding controls. This revealed four miRNAs linked to RA that were also identified by the MIGWAS pipeline, one of which was significantly highly expressed in RA patients.

"The analytical power of our approach shows its potential for finding new networks of miRNAs and their target genes linked to traits and diseases, in a tissue-specific way," corresponding author Yukinori Okada says. "This should make it easier to find new targets that we can focus on for developing therapeutic strategies for a wide range of diseases."

Explore further: Decoding the regulation of cell survival—a major step towards preventing neurons from dying

More information: Saori Sakaue et al, Integration of genetics and miRNA–target gene network identified disease biology implicated in tissue specificity, Nucleic Acids Research (2018). DOI: 10.1093/nar/gky1066

Related Stories

Aqueous humor, microRNAs and glaucoma

April 11, 2018

Glaucoma—the leading cause of vision loss worldwide—includes a heterogeneous group of disorders. Primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG) are linked to decreased outflow of aqueous humor, which ...

Recommended for you

Machine learning identifies links between world's oceans

March 21, 2019

Oceanographers studying the physics of the global ocean have long found themselves facing a conundrum: Fluid dynamical balances can vary greatly from point to point, rendering it difficult to make global generalizations.

How fluid viscosity affects earthquake intensity

March 21, 2019

Fault zones play a key role in shaping the deformation of the Earth's crust. All of these zones contain fluids, which heavily influence how earthquakes propagate. In an article published today in Nature Communications, Chiara ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.