May 15, 2017 –
Yale scientists publish a study in Nature that shows how WuXi NextCODE's AI and genomic analysis technology revealed an unknown cause of cardiovascular disease.
WuXi NextCODE today highlighted the contribution of its artificial intelligence (AI) and sequencing teams to the discovery of a novel mechanism regulating how blood vessels grow. The study, “FGF-dependent metabolic control of vascular development,” led by Yale University’s Michael Simons and including scientists from six countries, is published in the May 2017 edition of Nature.
The development of blood vessels is regulated by growth factors. If this development is impaired it can lead to cardiovascular disease; conversely if it is normal or upregulated in cancer, it can contribute to a tumor’s rapid growth.
To investigate the little-understood role in vascular development played by a family of growth factors called fibroblast growth factors (FGFs), Dr. Simons and his team studied mice with the genes encoding FGF receptors knocked out. The mice had reduced vascular development according to a number of criteria, demonstrating for the first time that FGFs play an important role in blood vessel growth.
This was itself a discovery, but it didn’t explain how FGFs influence this process – a challenge that involved mapping out largely unknown pathways through large sets of complex biological data.
“What WuXi NextCODE’s analysis helped to solve was the identification of the molecular mechanism responsible for the FGF phenotype we observed: it clearly showed FGF involvement in control of metabolic pathways in the endothelium,” said Dr. Simons, the Robert W Berliner Professor of Medicine and Biology at Yale.
“The fact that FGF controls the metabolic process of glycolysis was not known before this study and was a complete surprise. WuXi NextCODE’s bioinformatics and tools provided an important insight into this previously unknown and important aspect of FGF biology. This discovery likely has clinical therapeutic implications, either to upregulate the pathway to address cardiovascular disease or to downregulate it in cancer to starve tumors of blood and food.”
The fact that FGF controls the metabolic process of glycolysis was not known before this study and was a complete surprise
WuXi NextCODE answered the challenge through its global platform, with coordinated efforts between its Shanghai and Cambridge teams. The company’s CTO Dr. Hongye Sun and his team in Shanghai sequenced the RNA produced by stimulated cells in the lining of the blood vessels of the knockout mice.
Dr. Tom Chittenden, WuXi NextCODE’s VP of statistical sciences and leader of its Advanced AI Lab, and his team then used their own sophisticated statistical technique, a nested gene ontology analysis, to tease out connections between RNA sequence variation, expression levels, molecular function and cell location according to key terms.
As they expected, this highlighted pathways linked to cell proliferation and migration. But quite unexpectedly, the results also showed enrichment of genes for glucose metabolism processes. Doctors Sun and Chittenden are co-authors on the study.
“AI enables us to derive even more value from our genomics platform by mapping the complex underlying biology of disease,” said Hannes Smarason, CEO of WuXi NextCODE. “This work is an excellent example of yet another application of this technology to advance knowledge and potentially point the way to new drugs to treat some of our biggest health challenges.”