From the Depths of Disease to the Depths of Space

AGBT Guest Blogger: Meredith Salisbury(Bioscribe)

February 12, 2016


By Friday afternoon here at AGBT, attendees were starting to show signs of wear from the all-

night parties, but they rallied for a plenary session featuring a couple of genomics veterans and a

project about sequencing in outer space.

Cancer research luminary Harold Varmus started things off with a talk on precision medicine and

its implications for understanding carcinogenesis. He began with a look at oncogenic mutations

that seem to be mutually exclusive, such as EGFR and KRAS, which are the most frequently

mutated oncogenes in lung adenocarcinoma but have never been observed in the same tumor.

Using transgenic mice, his team showed that inducing expression of one oncogene in the

presence of the other causes cell death, leading to the intriguing if uneasy possibility of using an

oncogene as a potential therapeutic. In other work, Varmus’s lab is investigating mutation

frequency in splicing factor genes, which may be related to carcinogenesis. They’re now using

CRISPR/Cas9 experiments to determine why such high mutational frequency is seen in cancer


If attendees needed a dose of adrenaline to power through the day, they got it in the form of

Chris Mason’s breakneck-pace presentation about an integrative ’omic study of twin astronauts

he’s doing for NASA. The two-year-long study measures virtually everything that can be

measured, from proteomics to DNA mutations to methylation patterns and telomere lengths and

more, in both twins for the year while one is at the International Space Station and the other is

earthbound, plus six months before and after the mission. Mason said that some people view the

project as a publicity stunt, but it’s actually an early and important step in NASA’s long-term

goal of having “boots on Mars” by the mid 2030s. (Session host Eric Green wasted no time in

announcing the red planet as the location for AGBT 2036.) Mason described logistical

challenges of the project, such as recovering blood samples sent back from space on a capsule

and testing an Oxford Nanopore MinION in a zero-gravity simulator to prepare for sequencing in

space. He also shared some data from 10x Genomics’ Chromium system, which allowed his

team to assemble very long DNA fragments from short-read sequence data.

Debbie Nickerson wrapped up the session with a nice overview of progress in tracking down the

genetic causes of Mendelian diseases. While the community has solved more than half of the

7,400 rare Mendelian phenotypes described in OMIM, Nickerson noted that 300 new phenotypes

are identified each year, so it’ll be important to scale up efforts to generate answers. Causative

variants can be especially hard to find when diseases are vanishingly rare, highly heterogeneous,

or based on multiple variants acting in concert. She shared several examples of projects

completed by the Centers for Mendelian Genomics, which collaborate with hundreds of

investigators around the world and have made even more new genetic discoveries. Nickerson

continued a key theme of this meeting — the need for better data sharing — with examples of

new initiatives to make it easier for scientists and also for parents to share genomic and

phenotypic data.