Precision medicine for understudied populations

by Roxana Daneshjou, guest contributor

Precision medicine, which leverages a patient’s genetics to help make medical decisions, has the potential to revolutionize medicine. Its applications are numerous: from predicting who may have an adverse reaction to a medication, to allowing targeted therapies of cancer with particular mutations. In 2015, President Obama’s State of the Union announced an initiative to further our understanding of precision medicine and to build the infrastructure to implement it. An important part of this initiative is building a large diverse research cohort to help discover disease-gene and drug-gene associations. The key word is diverse – because genetic risk factors can be population-specific. In the past, individuals of African, Hispanic, and Middle Eastern ancestry have been understudied. Only by including individuals from all different ancestral backgrounds can we hope to implement precision medicine in an inclusive way.

In 2011, Russ Altman’s research group was pondering the importance of inclusive precision medicine when it became clear that several studies examining the baseline genetic variation across the globe, 1000 Genomes and the International HapMap Project, had an underrepresentation of Middle Eastern populations. As a scientist of Iranian descent who had undergone direct-to-consumer genotyping with 23andMe, I wondered how to make sense of my data when no baseline genetic study of the Iranian population existed. When scientists Dr. Mostafa Ronaghi and Dr. Pardis Sabeti approached Dr. Altman’s group about the idea of creating such a baseline, I was immediately interested. Through the generous support of the PARSA Foundation, we began our journey to create a genetic baseline of the Iranian population.

Our first roadblock appeared when we spent months exploring the feasibility of collecting samples in Iran. Due to the economic sanctions at that time, it turned out that establishing a collaboration with an Iranian university and collecting samples there would be nearly impossible. In the United States, however, the Iranian diaspora has created a sizeable population generally representing the diversity of sub-ethnic groups in Iran.  We turned to this population to collect our samples and conducted high coverage sequencing of 77 healthy individuals. This data can be used for answering some questions about the population’s history and also as a baseline for scientists interested in studying disease in this population.

Since our aim is to enable other scientists to answer important questions about disease risk and treatment in individuals of Iranian ancestry, we are committed to sharing our data. Our website, irangenes.com, already has summary data of population level genetic variants. We’re currently working on uploading all of our genomic data on a secure server so that scientists can submit proposals to use our raw data.  Since the sanctions on Iran were lifted in January 2016, we have corresponded with scientists in Iran who are using our summary data to help advance precision medicine there. We are also working on uploading all of our genomic data to a secure server as a part of the precision medicine initiative so that scientists can submit proposals to use our raw data.

In addition to the medical applications, we were also interested in learning more about the Iranian population’s history through its genetics. Based on our data, the Iranian population is genetically distinct from other Middle Eastern populations. However, it is important to remember that any two humans share 99.9% of their genome. Moreover, as has been seen in previous studies in other populations, the different Iranian sub-ethnic groups have a lot of genetic overlap. Though capturing the breadth of human genetic diversity is important to inclusive precision medicine, these studies also show us that – at our core – we are a singular human family.

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Roxana Daneshjou is an MD/Ph.D. student at Stanford and is supported by the Paul and Daisy Soros Fellowship for New Americans.

New Genetic Spectra Across Earth’s Cities & Far Beyond

by Chris Mason, guest contributor

Since speaking at TEDMED 2015, there have been a number of updates to the science I described in my talk. These areas include: space genomics, beer-omics, extreme microbiomes, global city metagenome sampling, epitranscriptome discoveries in RNA viruses, and DNA as music in microgravity.

Image based on images courtesy of ShutterstockSpace Genomics and Genomic DJs

First, we have completed the first whole-genome sequencing profile of two astronauts’ genomes (the Kelly Twins). Also, in collaboration with our NASA collaborators, (Aaron Burton and Sarah Castro-Wallace) we have been sequencing DNA in microgravity; this will be used for 2016 plans to send an Oxford Nanopore Sequencer onto the International Space Station with astronaut Kate Rubin. We are preparing for the return of astronaut Scott Kelly to Earth next week, and are strategizing how to make genome-guided medicine a part of the standard of care for new astronauts. Our goal is to monitor, protect, and potentially repair astronauts’ biology through an integrated view of the layers of the genome, transcriptome, proteome, all the epi-omes, and the microbiome.

In collaboration with Harvard Medical School’s Consortium on Space Genetics, we’ve formally launched a new research focus for Weill Cornell medical students on the study of space genetics and aerospace medicine. This allows new medical students to learn and train in the methods of space genomics, data analysis, and new technology development for space missions. They’re also trained in synthetic biology, materials science, nanofabrication, microbiome engineering, and gene drives. These skills are taught in our class called “How to Grow Almost Anything (HTGAA) – NYC” that is part of the BioAcademany. Work by Elizabeth Hénaff in the 2015 class also helped with our plan for the Gowanus Canal and extreme microbiomes.

Extreme Microbiomes

Microbiomes can lead to a bounty of discovery for new biology, drugs and molecules. We have been systematically hunting for these microbes around the world as part of the eXtreme Microbiome Project (XMP). Among those sampled sites, we have already found that Brooklyn’s Gowanus Canal, a SuperFund site, holds a suite of unique and potentially protective microbes, and we have been designing artificial sponges to hold these in the canal during the remediation process. This is part of a larger project of urban microbiome monitoring and design, called the Brooklyn Bioreactor, which is a collaboration between our laboratory at Weill Cornell, the landscape architecture firm Nelson Byrd Woltz, the Gowanus Conservancy, and the community laboratory Genspace. Lastly, in collaboration with Shawn Levy at HudsonAlpha, we have started collecting data about beer microbiomes, which show an interesting blend of differences depending on the yeast strain used.

Global Metagenome Collection Day

The Metagenomics and MetaDesign of Subways and Urban Biomes Consortium has now reached 43 cities around the world, and a global City Sampling Day (CSD) event is planned for June 21, 2016, to match the collections of the global Ocean Sampling Day (OSD) group. These seasonal molecular snapshots will begin to expand our search for novel microbiomes, new molecules, will aid us in mapping the distribution of antimicrobial resistance (AMR) markers, and enable a better understanding of urban biology and ecosystems.

Epitranscriptome Discoveries and Sounds of RNA

Last but not least, we have just published the first demonstration of another realm of RNA modifications, collectively called the “epitranscriptome.” Specifically, we show that HIV’s RNA genomes also harbor modified RNA bases, and they impact how infectious the virus may be for a patient. We are now on a search across all RNA viruses to see how common these types of modifications are. We are also working to get direct RNA sequencing in nanopores operational, to enable listening to the “music” of the genome as it moves through the pore, as we demonstrated was possible with single enzymes in 2012. These methods and algorithms can help us discern new and peculiar nucleic acids that might be found not only in our lab, but in far-flung places on Earth and beyond.

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In his TEDMED 2015 talk, geneticist and urban metagenome researcher Chris Mason of Weill Cornell Medicine shares how he’s mapping his expertise into the distant future of outer space in the interest of humanity’s interplanetary survival.