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SCIENCE SPOTLIGHT
Mix and Match with MixOmics Analyses
Cheryl S. Rosenfeld, DVM, PhD

Various ’omics approaches are in widespread usage in DOHaD research. Integration of ’omics data and phenotypic data, such as metabolic, behavioral, or immunological assessments is important to  establish mechanistic cause and effect relationships between in utero or perinatal exposures and later health outcomes, the major tenet of the DOHaD concept. To integrate such omics and phenotypic data, one of the most useful programs created to date is the mixOmics R package (mixomics.org) (1). This package allows for visualizing both high level correlations between multiple omics datasets (such as the DIABLO, Data Integration Analysis for Biomarker discovery, plot)  and “digging into the weeds” approach to identify specific markers that are correlated, and determine directionality and magnitude of change (such as the circos plot). We have shown that this is an effective tool for integrating the developmental effects of the endocrine disrupting chemicals (EDC), bisphenol A (BPA) and genistein on gut microbiota and fecal metabolome expression changes and host neurobehavioral responses (2, 3). This program has also been used to link BPA-induced changes in placental gene expression, metabolome, neurotransmitter concentrations, and histopathological changes to show that reductions in placental serotonin seen in the BPA-exposed mouse placenta correlate with reductions in certain trophoblast cells (4). Furthermore, mixOmics analyses permitted my group to extend the findings of a recent CLARITY-BPA consortium study [13 independent investigators within the U.S. who collaborated with the Food and Drug Administration (FDA)/National Center for Toxicological Research (NCTR) (5)] to successfully apply a systems biology approach to reveal strong organismal relationships of both positive and negative associations at three different ages and dosages for time points: 21 days of age (weaning), 90 to 120 days of age (young adult), and 6 months of age (older adult). These studies demonstrate that mixOmics analyses can be used to integrate complex multi-omics and phenotypic datasets, however, it cannot prove the sequence of changes or establish causation. This still requires follow-up studies to pinpoint and define the order of biomolecular and phenotypic changes induced by developmental exposures.
MEMBER HIGHLIGHTS

Dr. Suzanne (Sue) Fenton is the Group Leader in Reproductive Endocrinology in the National Toxicology Program Laboratory, at the National Institute of Environmental Health Sciences. Her BS, MS, and PhD are from the University of Wisconsin-Madison, where she trained in Dairy Science/pre-vet, Gamete Biology, and Lactation Biology. She was a post-doctoral fellow at the Lineberger Cancer Center, at UNC-Chapel Hill prior to starting her own research lab at the US EPA. Sue began her independent research by defining critical windows of development during which the mammary glands of the fetus and the pregnant dam were sensitive to environmental chemicals. She continues to characterize the effects of endocrine disruptors on mammary and placental tissue, and how that may affect the fetus/newborn.  Her current work is strongly focused on emerging chemicals, especially some of the poorly characterized perfluorinated chemicals in the drinking water of NC communities. In her free time, Dr. Fenton enjoys spending time with her grandson, Jack, who was a silver lining during the COVID-19 research shut-down.

Dr. Amara Finch is an intern in the combined Internal Medicine-Pediatrics Program at the University of Arizona and recently joined the US-DOHaD chapter.  Her training began at Yale University, where she studied Ecology and Evolutional Biology, followed by medical school at Emory University.  When asked how she became interested in the area of DOHaD she explained, “For as long as I can remember, I've been very interested in thinking about how early life affects lifelong health. During high school, I became interested in the relationship between human evolution and our species' vulnerability to various diseases (as well as our resilience!). Throughout college I continued to explore these ideas, and became increasingly interested in the relationship between social determinants of health and how early life experiences shape our health and physiology for a lifetime. I credit my mentors in college, Dr. Steve Stearns and Dr. Rick Bribiescas, for helping me explore these interests and teaching me to think critically about the relationship between evolution, environment and health. During medical school, I was fortunate to work with Dr. Michelle Lampl and became passionate about the effects of early life growth patterns on lifelong health, and how these insights might be leveraged in the pursuit of health equity and breaking intergenerational cycles of poor health. I don't remember when I first heard the term "DOHaD", but once I did, I knew I had found an intellectual home.”  She aims to focus her career on the pre-conception period in order to optimize offspring health by working with adolescents and young adults, as well as by working with infants and children to optimize their health in light of their developmental past.  She aspires to create pediatric guidelines that incorporate our knowledge regarding early life trajectories to tailor growth goals and metabolic needs.  In her time off she enjoys hiking the beautiful Southwest, and working on perfecting her homemade hot sauce!   

OPPORTUNITIES
Click here for current post-doctoral fellowship opportunities in DOHaD related labs. 
Click here to learn more about the COVID-19 exposure study opportunity!
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