LOS ANGELES – Michael Snyder, PhD, wears his research on his sleeve, so to speak. On any given day, he wears up to eight devices on his body that measure everything from radiation exposure to fasting glucose and sleep activity.
The way he sees it,wearables to monitor physiomes, plus personal omics profiling technology, give a high-resolution view of how health changes over periods of wellness and disease.
“We know intuitively that your health state is influenced by many things, including your genome and all of the things you’re exposed to, from pathogens to food, stress, and exercise,” Dr. Snyder said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “They all impact your health state, but in a future not far away, people will be born with their genome sequenced, and we will understand in a probabilistic fashion how, with a set of variants in your genome, if you are exposed to certain environmental conditions, you will have certain health outcomes. As an example, if you’re at risk for Parkinson’s disease, you probably shouldn’t be a pesticide worker, because that greatly increases the chances by which you get Parkinson’s.”Snyder Lab in the department of genetics at Stanford (Calif.) University, and other researchers have been pushing to bring genomics to the clinic. Currently, individuals can have their genomes sequenced for about $850, “and that price is dropping even further,” he said. “There is a revolution going on in mass spectrometry where you can profile many thousands of molecules and bodily fluids like blood and urine, so we can analyze those in incredible detail. At the same time, many people are using wearable devices. We’re big believers in bringing all of this so-called big data together, trying to define what it means to be healthy and what happens when people transition to disease as we follow them over time.”
About 8 years ago, he and his associates launched an ongoing longitudinal personal omics profiling project of 105 individuals, 55% of whom are prediabetic. After undergoing genome sequencing, each person undergoes measurement of 14 different omics every 3 months, including their RNA, proteins, lipidomics, cytokines, and microbiome (Cell Host Microbe. 2014 Sep 10;16:276-89).
When a perturbation comes along, like a viral infection or positive results from a colonoscopy, the researchers gather additional samples. “We are trying to understand how the different omics relate to one another,” said Dr. Snyder, who in 2012 used his own genome sequence to predict and help diagnose his own type 2 diabetes, a story that received international media attention. “If you know the inputs into a system, you should be able to calculate the outputs, no matter how complex the system is. You should be able to make meaningful associations. In this case, the inputs are your genome, your epigenome and your microbiome, and the foods you eat. The outputs would be the metabolome, and things like that. We try to understand how responses to, say, viral infections or other perturbations are similar to one another, like congestion and fever, but also why some people get more ill than others, or have varying disease-specific symptoms.”
To date, Dr. Snyder and his associates have collected about 1,800 time points and roughly 10,000 samples. The first 1,000 of those time points have been analyzed. Of the first 70 people who underwent genome sequencing, 12 had pathogenic mutations that are clinically actionable, including mutations in BRCA1, which is associated with breast and ovarian cancer; APC and MUTYH, which are associated with colon cancer; SHBD, which is associated with a high frequency of neuroendocrine tumors; and RBM20, which is associated with dilated cardiomyopathy. One such person “underwent stress testing, and it turns out he does have a heart defect,” noted Dr. Snyder, who is also the author of Genomics and Personalized Medicine: What Everyone Needs to Know (New York: Oxford University Press, 2016). “So some of this information is extremely valuable. This is why we argue that genome sequencing, much like family history, will one day move into the clinic for those who want to use it.”
So far, the longitudinal personal omics analysis has revealed other important diagnoses that likely would have flown under the radar of conventional Western medicine, including a heart defect in one person that was detected by a simple wearable device, a case of early lymphoma, and a case of MGUS (monoclonal gammopathy of unknown significance), which is a precancerous condition.
“We have also had many metabolic cases; a lot of folks were prediabetic and others were diabetic,” Dr. Snyder said. “It’s hard to predict exactly what you’re going to see for any one person. But when you collect a lot of this data, you do find things that are important for their health.”
Of the current study participants, 23 underwent a dietary perturbation. Of these, 13 were insulin resistant and 10 were healthy controls, matched for body mass index. The subjects consumed an extra 1,000 calories per day for 30 days, maintained their peak weight for 7 days, and embarked on a weight loss program for 60 days. “We looked at the effects of weight gain and weight loss in incredible molecular detail,” Dr. Snyder explained, noting that the work will appear in a forthcoming edition of Cell Systems. “At baseline, we can tell the insulin-resistant from the -sensitive folks. After people gain and lose weight, we can identify all the compounds and biochemical pathways that change by using integrative c-means clustering to identify pattern recognition across RNA sequencing, proteome, metabolome, microbiome, and cytokines. From blood, we can actually see these compounds changing. We also can tease out differences between resistance and sensitivity in their reaction to weight gain and weight loss. For example, in the microbiome, the insulin-resistant folks were more resistant to changes in weight gain and weight loss, while insulin-sensitive folks go up and down pretty well.”
The researchers also observed that the omics profile of each person who participated in the dietary perturbation study was different at baseline. “So everybody is special, and not just to our mothers,” Dr. Snyder said. “That is to say, if I profile you, you will not look like anyone sitting next to you. If you go through a perturbation, you will still look more like you than the person sitting next to you.” Going forward, he predicted that personal omics profiling “will build a personal dashboard that relays into your smartphone and can measure your health. Just like your car dashboard, we hope that you’ll have indicators of health, which will be your command center of the future.”
He disclosed that he is a scientific adviser to Personalis, Genapsys, SensOmics, and Qbio.