Going beyond sequencing
Perhaps what surprised many about Wang’s move was that it came at a point when BGI seemed poised to take over the sequencing world. Since breaking even in 2011, the company has made aggressive moves to expand, accumulating a string of illustrious collaborators like the Bill & Melinda Gates Foundation along the way.
But BGI’s meteoric rise was not universally welcomed, especially by its competitors. Illumina, which at the time held 70 percent of the market share for next-generation sequencers, was so concerned by BGI’s 2012 decision to acquire US-based instrument and software provider Complete Genomics that it launched an unsolicited counteroffer for the ailing company.
When the offer was not accepted, Illumina’s CEO Jay Flatley then appealed to the Committee on Foreign Investment in the United States (CFIUS), attempting to block the sale on the grounds that putting Complete Genomic’s sequencing technology
into Chinese hands would amount to a threat to national security. These concerns were eventually dismissed, and the merger was completed in 2013. (BGI was previously Illumina’s top customer!)
The considerable financial, regulatory and legal hurdles BGI overcame to acquire its own sequencing technology underscored the company’s determination to become more than a service provider. In fact, as the company continued to grow, Wang and others were struck with the realization that simply knowing the DNA sequence was insufficient.
“We’ve made incredible progress with sequencing data and learnt so much about different diseases from genomic information. But sequence alone does not explain everything,” he says.
“Just to give you an example, we have discovered about 40 gene loci associated with type 1 diabetes, but these only explain about six percent of the cases. The remaining 94 percent of the predictability is missing; it’s just dark matter.”
Superheroes in our midst
The inadequacy of sequencing data has a personal dimension for Wang. Probably one of the most accurately sequenced human beings in the world, Wang discovered that he was a carrier of a gene for a lethal disease while running his own samples at BGI’s sequencing facilities.
Concerned, he did further research and found that the initial study had predicted the variation—a single nucleotide polymorphism (SNP)—to be lethal based on 300 Caucasian patients. When he examined a Chinese population, however, about half the people were found to share the same mutation.
“It was such a relief as clearly half the Chinese population does not have the disease,” he says, laughing. “That just tells us one thing: Even if a SNP has a strong association with a disease, it may have totally different indications in a different population background.”
One possible explanation, Wang says, is that certain people may have ‘superhero’ genes—genes that protect them even though they may carry other genes strongly linked to deadly diseases. In a study of over half a million people, BGI and iCarbonX scientists identified 13 individuals carrying inherited genes which should have caused serious monogenetic disorders such as cystic fibrosis but mysteriously were disease-free.
“No one is really perfect, but everybody is special; everyone has their own unique genome. A few extremely rare individuals have these extreme ‘superhero’ phenotypes, but we can only identify them if we have a large enough number of individuals,” Wang says.
“What we need is more data—much more data.”