AGBT 2017, a Mix of Single Cell Genomics, Long Read Technology, and More

This year’s meeting followed the true and tested script of past AGBT installments. Similarly to last year’s conference, the technological advancements seemed to have slowed and somewhat resulting in no breakthrough announcements, while a larger emphasis was put on the scientific talks. Software analysis announcements related to secondary and tertiary sequence data analysis solutions were almost not present.

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Interestingly, the much liked software demo session was mostly reduced to three open source demonstrations and a demonstration of Optalysys, a light-based sequence alignment technology. Too bad, as the software demo part provided a great opportunity to get up to speed with the latest developments across the many commercial solutions available on the market. Something that was the opinion of the wider audience, as there are an overwhelming amount of software solutions available that seem similar in nature yet provide very specific capabilities.

As it has been the case last year, the trend is now for companies to announce major updates and product news in the beginning of the year, at the JP Morgan conference, seemingly turning the AGBT conference more into a scientific applications conference. Here, I am summarizing some of the news that accompanied this year’s AGBT conference, plus a couple of talk highlights.

Talk highlights

Zika: Oliver Pybus (University of Oxford) provided a talk on the genomic evolution and epidemiology of the Zika virus in the Americas. Interestingly, by the time they had sequenced one Zika genome – an 11kb single-stranded RNA vector (mosquito-borne) virus – already over 30 million infections had been projected in Brazil alone, with the first confirmed transmission dating from April 2015. By now, the group has sequenced a grand total 20 genomes from Northeast Brazil that has a relatively high risk for Zika occurrence and transmission. The epidemic is caused by a lineage of the Asian Zika genotype as opposed to the African genotype. Challenges associated with the Zika virus detection: the virus copy number in clinical samples is often very low, and only detectable for about two days. Pybus then talked about the Zika virus in Florida, the only place in the US with large-scale local transmissions, most certainly imported via travel cases (~250 known local cases across Florida in 2015). His team has now sequenced 40 genomes which are estimated to represent about 10% of the Zika population. It is suggested that the virus most likely came into Florida from the Caribbean via cruise ships.

The current goal is to better characterize the Zika virus diversity. Towards this end a mobile lab, the so called “Zika bus”, is traveling to regional medical centers helping with the massive back log of clinical tests.

Virome project:  Eddy Rubin (Metabiota) talked about the fascinating global Virome project. He did start out by talking about the “father of epidemiology”, John Snow, who created the “The Ghost Map” to study the outbreak of Cholera in London. He identified that outbreaks were clustered around water sources, suggesting that a water-borne agent is causing the disease which ended the cholera epidemic. Rubin detailed the Virome project and its goal which is to collect data in waterfowl breeding sites with high mammal diversity with the aim to convert virology to a data-rich science.

We now seem to face an epidemic outbreak of some sort each year, whether it is MERS, Zika, or Ebola, and one wonders what’s next and where do these viruses come from? Clearly close interactions of humans with wildlife results in opportunities for species to species transfers, which is thought to have contributed to such a dramatic increase in the last two decades. Considering we continue to see a substantial population increase in many regions of the world, and an increase in human-animal contact, the impact is bound to be getting bigger and bigger.

Virome project’s specifics:

  • Cost:
    • $1B
    • Currently virology seems to be a “mom & pop industry” (quote Rubin), and the idea is that the Virome project should bring it to a data-rich field.
  • Aim:
    • To look at specific regions with larger viral populations
    • To create a vaccine against a family of viruses and their core proteins (The thought is if you have 10K corona viruses – you can create a vaccine against the family and core proteins)
    • To build capacity for detection and response
    • To respond to outbreak as quickly as possible, as they are like fires
    • To define metrics and goals and potential best practices how virologists operate
    • To think proactively and not only react after an epidemic has started

Rubin completed his talk with a remark that John Snow would view the world, as it is today, as dangerous.

Cholera: One of my favorite talks was by Rita Colwell (University of Maryland and CosmasID) who provided some amazing insights into cholera. Cholera today is not the same threat anymore as the cholera from the past, and yet it is still highly relevant (e.g. Haiti). Cholera, an acute water-related diarrheal disease, today occurs in 50 countries and is still affecting 70 million people (the 7th pandemic only started in the sixties). The Bengal delta is known as the “native homeland” of cholera and as such it is highly unlikely that we will ever eradicate cholera completely. We also see an emergence in new subtypes, but those can mostly be controlled via secure global drinking water sources.

Today in the 21st century, we see a mix in populations, e.g. diarrheal patients with cholera symptoms have 10 plus bacteria in their stool. Colwell is applying metagenomics to study the cholera epidemics in Kolkata, India. Interestingly, they noted that Indian diarrheal patients that are diagnosed with cholera were in addition also carriers of four to ten enteric pathogens. Yet, these patients are not getting as sick as Westerners would which is suggested to be attributed to the amount and frequency of yogurt and buttermilk in their diet – a counter-healthy bacterial population. As such, the microbiome of the Indian gut is much different from the Western gut allowing them to tolerate some of the pathogens that Westerns have a hard time coping with.

The study of bats: One talk that left an impression on most attendees was Emma Teeling’s (University College Dublin) whose focus was on comparative genomics of bats. Her main research interest seems to lie in understanding longevity and extended life/health span. “We know aging, but we do not understand it!”

Teeling pointed out that bats seem to be excellent study objects for this purpose as high metabolism, them being carriers of viruses – Ebola, rabies, SARS, MERS – and yet they don’t seem to get sick, and they break the rule of body mass vs. longevity (big is usually associated with longer life span) while living over 40 years. Furthermore, one in five creatures alive are bats! It almost sounds like “life in the fast lane” is the right approach for longevity! It turns out that only 0.1%, a low diversity of bat genomes, have been sequenced, but there are currently >1,000 species of bats. Teeling and her team decided to get together with other researchers and sequence them all. The bat genome is a small genome of ~2GB and ~22K genes. A drawback is that the longest living bats do not live in captivity at all. Their approach is to study a bat population in Mont St. Michel which the researchers now visit every year, since ten years. The scientists have tagged the bats and need to capture them again and again over time for blood sample and wing punches collection. At this point, their collection boasts over 300K wing punches and by now the researchers have a pretty good picture of the bat family structure (mother, daughter, population degree, etc.). Preliminary findings indicate that telomere shortening is much reduced compared to other animals (based on a qPCR methodology) and little to no correlation of age with shortening of telomeres is observed. There is still a lot to be researched to understand longevity and aging and we will see if the bats will be able to tell us more.

Listen to her TED talk: The secret of the bat genome.

Announcements accompanying the conference

Announcements at this year’s AGBT were rather sparse in nature but included:

  • Cofactor Genomics launched Pinnacle: a CAP-CLIA Certified RNA-Based oncology assay. Cofactor Pinnacle utilizes the company’s software technology to compare each patient’s cancer expression profile to Cofactor’s database of thousands of expression profiles from the same cancer type. The assay reports on both aberrant oncology-relevant gene expression and known cancer gene fusions detected in the tumor sample.