Journal Article

Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration

Moremen, Kelley W., Chapla, Digantkumar, Bao, Bokan, Liang, Chenguang, Mohammad, Mahmoud A., Lewis, Nathan E., Haymond, Morey W., Richelle, Anne, Koga, Natalia, Fürst, Annalee, Bruntse, Anders Bech, Chiang, Austin W. T., Najera, Julia A., Yang, Jeong-Yeh, Bode, Lars, Kellman, Benjamin P.

2022

Overview

Human Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we use a systems biology framework that integrates glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we construct models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. Our model aggregation approach recovers 2 of 2 previously known gene-enzyme relations and 2 of 3 empirically confirmed gene-enzyme relations. The top genes we propose for the remaining 5 linkage reactions are consistent with previously published literature. These results provide the molecular basis of HMO biosynthesis necessary to guide progress in HMO research and application with the goal of understanding and improving infant health and development. Human milk oligosaccharides are fundamental to infant health. Here the authors deploy a multi-omics systems biology approach to elucidate their biosynthetic network, including the associated enzymes and likely structures of ambiguous oligosaccharides.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38 / 631/45/1268 / 631/553/2710 / 631/92/72/1205 / 82/16 / Biology / Biosynthesis / Breast milk / Carbohydrates / Elongation / Enzymes / Gene expression / Genes / Glycan / Glycosyltransferases - genetics / Glycosyltransferases - metabolism / Humanities and Social Sciences / Humans / Infant / Infants / Mammary gland / Mammary glands / Milk / Milk, Human - metabolism / multidisciplinary / Oligosaccharides / Oligosaccharides - metabolism / Science / Science (multidisciplinary)