The TaxUMAP atlas: Efficient display of large clinical microbiome data reveals ecological competition in protection against bacteremia.

Longitudinal microbiome data provide valuable insight into disease states and clinical responses, but they are challenging to mine and view collectively. To address these limitations, we present TaxUMAP, a taxonomically informed visualization for displaying microbiome states in large clinical microbiome datasets. We used TaxUMAP to chart a microbiome atlas of 1,870 patients with cancer during therapy-induced perturbations. Bacterial density and diversity were positively associated, but the trend was reversed in liquid stool. Low-diversity states (dominations) remained stable after antibiotic treatment, and diverse communities had a broader range of antimicrobial resistance genes than dominations. When examining microbiome states associated with risk for bacteremia, TaxUMAP revealed that certain Klebsiella species were associated with lower risk for bacteremia localize in a region of the atlas that is depleted in high-risk enterobacteria. This indicated a competitive interaction that was validated experimentally. Thus, TaxUMAP can chart comprehensive longitudinal microbiome datasets, enabling insights into microbiome effects on human health.
Competing Interests: Declaration of interests J.S. is cofounder of Postbiotics Plus Research LLC. J.U.P. reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics; reports consulting fees from DaVolterra, CSL Behring, and MaaT Pharma; serves on an Advisory board of and holds equity in Postbiotics Plus Research LLC; and has filed intellectual property applications related to the microbiome (reference numbers #62/843,849, #62/977,908, and #15/756,845). M.-A.P. received honoraria from AbbVie, Bellicum, Celgene, Bristol Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; served on data safety monitoring boards for Cidara Therapeutics, Servier, and Medigene; served on scientific advisory boards for MolMed and NexImmune; has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec; and has served as a volunteer for and as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be The Match (National Marrow Donor Program), and on the Center for International Blood and Marrow Transplant Research Cellular Immunotherapy Data Resource Committee. A.S.B. is on the advisory boards of Caribou Biosciences and ArcBio, and has served as a paid consultant for BiomX and Guardant Health. M.R.M.v.d.B. has received research support and stock options from Seres Therapeutics and stock options from Notch Therapeutics and Pluto Therapeutics; has received royalties from Wolters Kluwer; has consulted, received honoraria from, or participated in advisory boards for Seres Therapeutics, WindMIL Therapeutics, Rheos Medicines, Merck & Co, Inc., Magenta Therapeutics, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Forty Seven Inc., Ceramedix, Lygenesis, Pluto Therapeutics, GlaskoSmithKline, Da Volterra, Novartis (Spouse), Synthekine (Spouse), and Beigene (Spouse); has IP Licensing with Seres Therapeutics and Juno Therapeutics; and holds a fiduciary role on the Foundation Board of DKMS (a nonprofit organization). E.G.P. has received speaker honoraria from Bristol Myers Squibb, Celgene, Seres Therapeutics, MedImmune, Novartis, and Ferring Pharmaceuticals and is an inventor on patent applications #WPO2015179437A1 (entitled “Methods and compositions for reducing Clostridium difficile infection”) and #WO2017091753A1 (entitled “Methods and compositions for reducing vancomycin-resistant enterococci infection or colonization”) and holds patents that receive royalties from Seres Therapeutics.
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