title: GUTSS: An Alignment-Free Sequence Comparison Method for Use in Human Intestinal Microbiome and Fecal Microbiota Transplantation Analysis.
abstract: BACKGROUND
  Comparative analysis of gut microbiomes in clinical studies of human diseases typically rely on identification and quantification of species or genes. In addition to exploring specific functional characteristics of the microbiome and potential significance of species diversity or expansion, microbiome similarity is also calculated to study change in response to therapies directed at altering the microbiome. Established ecological measures of similarity can be constructed from species abundances, however methods for calculating these commonly used ecological measures of similarity directly from whole genome shotgun (WGS) metagenomic sequence are lacking.
  
  
  RESULTS
  We present an alignment-free method for calculating similarity of WGS metagenomic sequences that is analogous to the Bray-Curtis index for species, implemented by the General Utility for Testing Sequence Similarity (GUTSS) software application. This method was applied to intestinal microbiomes of healthy young children to measure developmental changes toward an adult microbiome during the first 3 years of life. We also calculate similarity of donor and recipient microbiomes to measure establishment, or engraftment, of donor microbiota in fecal microbiota transplantation (FMT) studies focused on mild to moderate Crohn's disease. We show how a relative index of similarity to donor can be calculated as a measure of change in a patient's microbiome toward that of the donor in response to FMT.
  
  
  CONCLUSIONS
  Because clinical efficacy of the transplant procedure cannot be fully evaluated without analysis methods to quantify actual FMT engraftment, we developed a method for detecting change in the gut microbiome that is independent of species identification and database bias, sensitive to changes in relative abundance of the microbial constituents, and can be formulated as an index for correlating engraftment success with clinical measures of disease. More generally, this method may be applied to clinical evaluation of human microbiomes and provide potential diagnostic determination of individuals who may be candidates for specific therapies directed at alteration of the microbiome.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Mitchell J
authors.identifier: http://orcid.org/0000-0001-7554-5732
authors.initials: MJ
authors.lastname: Brittnacher
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, United States of America.|Seattle Children's Research Institute, Seattle, Washington, United States of America.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Hillary S
authors.initials: HS
authors.lastname: Hayden
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Radey
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Weiss
authors.affiliation: Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Damman
authors.affiliation: Division of Gastroenterology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Zisman
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, United States of America.|Seattle Children's Hospital, Seattle, Washington, United States of America.
authors.forename: David L
authors.initials: DL
authors.lastname: Suskind
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.|Department of Medicine, University of Washington, Seattle, Washington, United States of America.|Department of Immunology, University of Washington, Seattle, Washington, United States of America.|Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003424:Crohn Disease / Q000235:genetics / Q000382:microbiology / Q000628:therapy; D000069467:Fecal Microbiota Transplantation; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D019520:Living Donors; D008297:Male; D054892:Metagenome; D056186:Metagenomics; D016415:Sequence Alignment