QNAS

QnAs with Pardis Sabeti QNAS

Sandeep Ravindran, Science Writer

Pardis Sabeti received the 2017 National Academy of and really understand how the Sciences Richard Lounsbery Award in biology for her malaria parasites are changing groundbreaking work in computational genetics and to survive against our immune global health. A professor at , the system and the drug pressures , and the Howard Hughes Medical we put on them. Institute, Sabeti has developed computational meth- ods to detect genetic variants under , PNAS: In 2014 you published and has applied these methods to both humans and alandmarkScience article on pathogens. She has conducted pioneering genomic the human-to-human transmis- analyses of Ebola and Lassa viruses, and her work sion of the Ebola virus (4). How played an important role in tracking Ebola transmis- did that article come about, sion during the 2014 outbreak in West Africa. Sabeti and what was its significance? recently spoke with PNAS about her efforts to combat emerging diseases. Sabeti: In 2014 our group was working with our collaborators PNAS: How did you first get interested in computational in Sierra Leone and in Nigeria genetics? on a disease called Lassa fe- ver, which is a hemorrhagic ’ Sabeti: I ve always really liked math and solving puz- fever virus much like Ebola. Pardis Sabeti. Photograph by Morgan Miller zles with math. I really enjoyed my math courses in We had gotten a grant to set and courtesy of Pardis Sabeti. college at MIT [Massachusetts Institute of Technol- up surveillance in West Africa ogy], but I also wanted to impact human health. Ge- for infectious diseases. Star- netics really struck me because it is biology as tlingly, just at that time the Ebola outbreak was mathematical information. So it had all of the compo- declared in Guinea just across the border, and our nents of what I wanted to do. collaborators in Sierra Leone found themselves at the epicenter of the outbreak. We were trying to help PNAS: What have been some of the key applications them rapidly do diagnoses and call attention to the of the computational methods you developed to problem. We had developed a number of techniques detect genetic variants under evolutionary selection to sequence Lassa fever over the last few years, and in humans and in pathogens? we were able to use them to sequence the Ebola virus and generate the data in a matter of weeks (4). It Sabeti: In my graduate studies I really became in- showed that we could release this kind of data in terested in how we can mine data from the human real-time, and that we could potentially have an un- and find footprints of ancient evolutionary derstanding of transmission as well as identifying mu- adaption both in humans and in pathogens (1–3). Es- tations in the virus that might impact diagnostics and sentially, if a variant is important for the survival or re- therapies. The fact that we could show with data that productive success of an organism, it will be likely to be the virus was mutating also provided a greater push to passed on to that person’s children and to their child- move quickly. ren’s children, and as a result it will spread in the pop- ulation. I developed computational methods that allow PNAS: How are you continuing to combat pandemics, you to find the footprints of ancient evolutionary pres- such as Ebola and Lassa fever? sure and then used them to pinpoint specific mutations that have an important biological impact. The key ap- Sabeti: Over the course of the last few years, we’ve set plication of these kinds of methods is to find those up sequencing machines in Sierra Leone, Senegal, functional variations that are important for the survival and Nigeria, and we’ve partnered with colleagues of humans or the microbes that infect humans. These in Liberia to help their sequencing efforts there. Ev- methods have been used to track down variations in erysummerwebringsomeonefromeachofthose humans that are important in resistance to infectious countries to receive training in advanced sequenc- diseases, such as malaria. Interestingly, we can also ap- ing.Wealsohaveabout20peoplewhoareherein ply these same tools to track drug resistance in malaria summer getting foundational learning in molecular

www.pnas.org/cgi/doi/10.1073/pnas.1714015114 PNAS | September 12, 2017 | vol. 114 | no. 37 | 9757–9758 Downloaded by guest on October 1, 2021 diagnostics for these viruses. We continue to build PNAS: How have your diverse interests outside of the better diagnostics and an understanding of how laboratory (such as being the lead singer of the rock these viruses work and of host responses to these band Thousand Days) influenced your approach to viruses. science and research?

PNAS: What has surprised you the most during your Sabeti: I do have a number of passions, music being one research career? of the greatest ones. I often say that people underesti- mate the creativity that you need in science, and the rigor Sabeti: One of the biggest surprises was the discovery that you need in music or other creative endeavors. Both that Lassa fever might be important in our history. I was require you to be able to start with an exploratory phase, scanning the human genome with the International where you discover and think and imagine all of the Haplotype Map project using the test I had developed things that are possible, but then to get that out into the to try to find footprints of ancient adaptation (5–7). The world it takes a large amount of rigor, either to produce a first time I did this, the strongest signal we found was for a gene that’s critical for infection with Lassa virus. It was song with 80 tracks all in the right way, or to do all of a really exciting moment, recognizing that actually this the right controls and to test a hypothesis carefully. Music virus is circulating in West Africa, where we discovered is particularly important to me because in West Africa, the signal of selection, and might have been around where we work, music is also really meaningful for them. for a really long time. I think that was a major turning I sing with my African colleagues and write music with point in my career, so that’s probably one of the most them, and we even recently released an album of music meaningful surprises. together.

1 Sabeti PC, et al. (2006) Positive natural selection in the human lineage. Science 312:1614–1620. 2 Neafsey DE, et al. (2008) Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence. Genome Biol 9:R171. 3 Park DJ, et al. (2012) Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite. Proc Natl Acad Sci USA 109:13052–13057. 4 Gire SK, et al. (2014) Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 345:1369–1372. 5 International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796. 6 Andersen KG, et al. (2012) Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever. Philos Trans R Soc Lond B Biol Sci 367:868–877. 7 Sabeti PC, et al.; International HapMap Consortium (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449:913–918.

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