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A digital twin of the infant microbiome to predict neurodevelopmental deficits

  • Nicholas Sizemore
  • , Kaitlyn Oliphant
  • , Ruolin Zheng
  • , Camilia R. Martin
  • , Erika C. Claud
  • , Ishanu Chattopadhyay

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R2 = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (Mδ) and identify infants achieving poor future head circumference growth with ≈76% area under the receiver operator characteristic curve, 95% ± 1.8% positive predictive value at 98% specificity at 30 weeks postmenstrual age. We find that early transplantation might mitigate risk for ≈45.2% of the cohort, with potentially negative effects from incorrect supplementation. Q-nets are generative artificial intelligence models for ecosystem dynamics, with broad potential applications.

Original languageEnglish
Article numbereadj0400
JournalScience advances
Volume10
Issue number15
DOIs
StatePublished - Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 American Association for the Advancement of Science. All rights reserved.

Funding

Acknowledgments: We acknowledge the center for the Science of early trajectories (Set) at the department of Pediatrics, University of chicago, for providing resources and support. Funding: this study was partially supported by nih grants P30dK042086 (center for interdisciplinary Study of inflammatory intestinal disorders), R01hd105234 (e.c.c.), institutional support from the Biological Sciences division, and the resources provided by the Research computing center (Rcc) of the University of chicago. Author contributions: e.c.c., c.R.M., and i.c. procured funding and directed research. K.O., e.c.c., and c.R.M. collected data and processed raw samples to procure microbial profiles. n.S., R.Z., and i.c. developed the modeling framework and the software implementation. n.S., K.O., e.c.c., c.R.M., and i.c. interpreted results and wrote the paper. Competing interests: the authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Q-net models are available at the permanent links https://doi. org/10.5281/zenodo.7453696 and https://doi.org/10.5281/zenodo.7942501. complete software is available as a python installable application at https://pypi.org/project/qbiome/ (also deposited to a permanent repository, accessible as https://doi.org/10.5281/ zenodo.7459014), which includes installation notes, and examples to run the inference and computation of M\u03B4 risk for individual patients. Q-net models inferred for the key results in this study are available at the permanent links https://doi.org/10.5281/zenodo.7453696 and https://doi.org/10.5281/zenodo.7942501.

Funders
University of Chicago

    ASJC Scopus subject areas

    • General

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