Accurate prediction of absolute prokaryotic abundance from DNA concentration.

Journal: Cell reports methods
Published Date:

Abstract

Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by digital droplet PCR in clinical stool samples from individuals undergoing hematopoietic cell transplantation (BMT CTN 1801). Based on this correlation and additional measurements, we trained an accurate yet simple machine learning model for the prediction of absolute prokaryotic load, which showed exceptional prediction accuracy on an external cohort that includes people living with Parkinson's disease and healthy controls. We propose that, with further validation, this model has the potential to enable accurate absolute abundance estimation based on readily available sample measurements.

Authors

  • Jakob Wirbel
    Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117, Heidelberg, Germany.
  • Tessa M Andermann
    Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, NC, USA.
  • Erin F Brooks
    Department of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.
  • Lanya Evans
    Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, NC, USA.
  • Adam Groth
    Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, NC, USA.
  • Mai Dvorak
    Department of Biology, Stanford University, Stanford, CA, USA.
  • Meenakshi Chakraborty
    Department of Genetics, Stanford University, Stanford, CA, USA.
  • Bianca Palushaj
    Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA, USA.
  • Gabriella Z M Reynolds
    Department of Genetics, Stanford University, Stanford, CA, USA.
  • Imani E Porter
    Department of Genetics, Stanford University, Stanford, CA, USA.
  • Monzr Al Malki
    Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
  • Andrew Rezvani
    Blood and Marrow Transplantation and Cellular Therapy Unit, Stanford University School of Medicine, Stanford, CA, USA.
  • Mahasweta Gooptu
    Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Hany Elmariah
    Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Center, Tampa, FL, USA.
  • Lyndsey Runaas
    Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Teng Fei
    School of Resource and Environmental Sciences, Wuhan University, Wuhan, China.
  • Michael J Martens
    Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA; Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Javier Bolaños-Meade
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mehdi Hamadani
    Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Shernan Holtan
    Blood and Marrow Transplantation Section, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Rob Jenq
    Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
  • Jonathan U Peled
    Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York City, NY, USA; Department of Medicine, Weill Cornell Medical College, New York City, NY, USA.
  • Mary M Horowitz
    Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Kathleen L Poston
    From the Departments of Radiology (K.T.C., F.B.d.C.M., S.S., G.Z.), Electrical Engineering (E.G., J.M.P.), and Neurology and Neurological Sciences (A.B., K.L.P., S.J.S., M.D.G., E.M.), Stanford University, 1201 Welch Rd, Stanford, CA 94305; Department of Engineering Physics, Tsinghua University, Beijing, PR China (J.X.); GE Healthcare, Menlo Park, Calif (M.K.); and Subtle Medical, Menlo Park, CA (E.G.).
  • Wael Saber
    Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Leslie S Kean
    Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Pediatric Hematology and Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Miguel-Angel Perales
    Department of Internal Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY.
  • Ami S Bhatt
    Department of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA. Electronic address: asbhatt@stanford.edu.