2022
DOI: 10.1038/s41467-022-29867-4
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Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multi-omics integration

Abstract: 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 … Show more

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Cited by 40 publications
(26 citation statements)
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References 121 publications
(149 reference statements)
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“…Sialylation of GlcNAc residues is still insufficiently understood. Even in humans, the responsible enzyme is not yet fully known, with indications for ST6GALNAC6 35 .…”
Section: Lacdinac Is Widespread In Mos Of Artiodactyla Speciesmentioning
confidence: 99%
“…Sialylation of GlcNAc residues is still insufficiently understood. Even in humans, the responsible enzyme is not yet fully known, with indications for ST6GALNAC6 35 .…”
Section: Lacdinac Is Widespread In Mos Of Artiodactyla Speciesmentioning
confidence: 99%
“…HMO biosynthesis represents an ideal system to understand the effects of maternal genetics on milk composition via changes in gene expression, as gene expression from the relevant cell type (mammary epithelial cells) and HMO concentrations can be measured non-invasively in the same milk samples. Among 54 candidate glycosyltransferase genes 42 , eight genes had significant milk eQTLs in our data (Table S12), which we used to test for associations between maternal genotypes at milk eQTL tag SNPs and HMO concentrations. For five genes we observed an association between genotype and between 1 and 12 HMOs (Table S13; q-value<10%).…”
Section: Milk Gene Expression Correlates With Concentrations Of Human...mentioning
confidence: 99%
“…Maternal genetics play a strong role in shaping the concentration of HMOs 7 , sugars in milk that are not digested by the infant but promote the growth of beneficial microbes in the infant gut. HMOs are synthesized in the mammary gland by addition of monosaccharides to a lactose molecule, but the glycosyltransferases catalyzing these reactions are largely uncharacterized 42 . Secretor status, determined by the absence of a common nonsense variant in the fucosyltransferase 2 ( FUT2 ) gene, strongly predicts the concentration of certain HMOs, with the presence of some HMOs entirely determined by secretor status 7 .…”
Section: Introductionmentioning
confidence: 99%
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