Background. Recent evidence points to the importance of the initial colonization of the human body with microorganisms-the establishment of the microbiome-as a determinant of health outcomes throughout life. The metagenomic technological advances available for characterizing the human microbiome across large cohorts at multiple time points are rapidly out-pacing the computational tools needed to clarify patterns of assembly of the microbiome and investigate connections between observed patterns and health and disease. Network-based methods have immense promise for filling this critical gap, but there are major limitations in the available suie of network analytic tools. The identification of clinically relevant patterns in biological network, and in particular, temporally evolving networks, urgently requires novel methodological approaches. Candidate. Dr. Hoen is a computational epidemiologist mentored by a multidisciplinary team within the Institute for Quantitative Biomedical Sciences (iQBS) and the Geisel School of Medicine at Dartmouth College. With her PhD in infectious disease epidemiology at Yale University and her postdoctoral training in the Children's Hospital Boston Informatics Program/Harvard Medical School, she is extremely well qualified to successfully accomplish her proposed research and career development plan and transition to independence as a scientist in biomedical informatics with the support of this award. Dr. Hoen has an established, productive research background that has resulted in 26 peer-reviewed publications on her interdisciplinary research. Environment. iQBS and the Geisel School of Medicine offer the ideal environment for the proposed career development and research. A collegial intellectual environment, at the core of which is Dr. Hoen's exemplary team of mentors and advisors is bolstered by numerous state-of-the-art research centers and core facilities, including a world-class supercomputing facility. Regular research seminars address current advances in biomedical informatics, genomics and biostatistics, and frequent lecture series in informatics, genomics and medicine attract leading investigators from around the world. Career Development Plan. The goal of this proposal is to gain mentored research experience and career development activities in order to advance Dr. Hoen'career into that of an independent researcher in biomedical informatics. Dr. Hoen's previous research has focused on computational studies of the distribution and determinants of infectious disease risk. She has experience in the analysis of microbial genomic data (doctoral training) and in public health informatics (postdoctoral training). The proposed career development activities and mentored research experience would take Dr. Hoen's expertise to a new level in two distinct ways: (1) by providing her mentored research experience in the development, evaluation and application of novel tools for biomedical informatics research;and (2) by providing her training in biomedical informatics for clinical and translational research. Dr. Hoen proposes to participate in coursework, workshops, seminar series, and research meetings that focus on professional ethics, translational research methods, computational biology including genomics, metagenomics, network analysis, and systems biology. Dr. Hoen has assembled an exemplary mentoring team, led by Dr. Jason Moore, who has a longstanding history of mentorship, leadership, and funded research in biomedical informatics. Her team of mentors and advisors include internationally known experts on informatics methods development, network analysis and complex systems, computational analysis of metagenomic data, clinical and translational science, epidemiology and biomedical informatics leadership. The collective expertise embodied by this team will provide an outstanding resource for the development of Dr. Hoen's career and the successful execution of her multidisciplinary, translational research in biomedical informatics. Dr. Hoen's team is committed to ensuring that she achieves a successful mentored research and career development experience as she works toward independence within the timeframe of this award. Research Plan. The goal of the proposed research is to develop, evaluate and apply computational tools that capture the complexity of large, longitudinal datasets of microbial community composition in conjunction with rich clinical information from a unique ongoing large molecular epidemiologic study using a systems approach that focuses on the complex interactions between human hosts, the communities of bacterial taxa that comprise the microbiome, exposures, health and disease. The framework upon which this research will be built is a series of networks that represent the complex interactions between infants and microbial colonization patterns in light of early life exposures and health-related outcomes. The analyses proposed will address complex patterns captured by these networks including multi-scale associations, multi-way interactions between network components, and temporal dynamics in changing networks. The overarching hypothesis of this research is that these innovative approaches can reveal critical associations between microbiome composition and health and disease in early life. The translational potential of this research lies in novel opportunities to reduce disease risk through therapies that manipulate and preserve a healthy microbiome.

Public Health Relevance

The patterns of initial colonization of our bodies with microorganisms can have important effects on risk for common illnesses;however, the tools available to characterize these patterns are limited, and the complexity of this system presents a challenge scientific research. We aim to develop, evaluate and apply new analytical approaches to capturing and clarifying the complex interactions between humans, human-associated microorganisms, health exposures and disease risk. The results of this research will lead to advances in early- life preventative care and therapeutic interventions that support the communities of health-promoting microorganisms in our bodies.

National Institute of Health (NIH)
National Library of Medicine (NLM)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZLM1)
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Sim, Hua-Chuan
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Dartmouth College
Family Medicine
Schools of Medicine
United States
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Chernikova, Diana A; Madan, Juliette C; Housman, Molly L et al. (2018) The premature infant gut microbiome during the first 6 weeks of life differs based on gestational maturity at birth. Pediatr Res 84:71-79
Lundgren, Sara N; Madan, Juliette C; Emond, Jennifer A et al. (2018) Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner. Microbiome 6:109
Hoen, Anne G; Madan, Juliette C; Li, Zhigang et al. (2018) Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population. Sci Rep 8:12627
Gossai, Anala; Waterboer, Tim; Nelson, Heather H et al. (2016) Prospective Study of Human Polyomaviruses and Risk of Cutaneous Squamous Cell Carcinoma in the United States. Cancer Epidemiol Biomarkers Prev 25:736-44
Gossai, Anala; Waterboer, Tim; Hoen, Anne G et al. (2016) Human polyomaviruses and incidence of cutaneous squamous cell carcinoma in the New Hampshire skin cancer study. Cancer Med 5:1239-50
Wright, Peter F; Hoen, Anne G; Ilyushina, Natalia A et al. (2016) Correlates of Immunity to Influenza as Determined by Challenge of Children with Live, Attenuated Influenza Vaccine. Open Forum Infect Dis 3:ofw108
Wright, Peter F; Connor, Ruth I; Wieland-Alter, Wendy F et al. (2016) Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants. Lancet Infect Dis 16:1377-1384
Gossai, Anala; Waterboer, Tim; Nelson, Heather H et al. (2016) Seroepidemiology of Human Polyomaviruses in a US Population. Am J Epidemiol 183:61-9
Madan, Juliette C; Hoen, Anne G; Lundgren, Sara N et al. (2016) Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants. JAMA Pediatr 170:212-9
Chernikova, Diana A; Koestler, Devin C; Hoen, Anne Gatewood et al. (2016) Fetal exposures and perinatal influences on the stool microbiota of premature infants. J Matern Fetal Neonatal Med 29:99-105

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