title: Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences.
abstract: Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
authors: 1] Faculty of Computer Science, Dalhousie University, Halifax, NS, Canada. [2].
authors: Morgan G I
authors: MG
authors: Langille
authors: Jesse
authors: J
authors: Zaneveld
authors: J Gregory
authors: JG
authors: Caporaso
authors: Daniel
authors: D
authors: McDonald
authors: Dan
authors: D
authors: Knights
authors: Joshua A
authors: JA
authors: Reyes
authors: Jose C
authors: JC
authors: Clemente
authors: Deron E
authors: DE
authors: Burkepile
authors: Rebecca L
authors: RL
authors: Vega Thurber
authors: Rob
authors: R
authors: Knight
authors: Robert G
authors: RG
authors: Beiko
authors: Curtis
authors: C
authors: Huttenhower
mesh_terms: D001419:Bacteria / Q000145:classification / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D056186:Metagenomics / Q000379:methods*; D064307:Microbiota / Q000235:genetics; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D005819:Genetic Markers; D012336:RNA, Ribosomal, 16S
references: Nature. 2011 Oct 30;480(7376):241-4
references: 22037308
references: ISME J. 2013 Apr;7(4):830-8
references: 23235290
references: Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17726-31
references: 22006333
references: ISME J. 2012 Mar;6(3):610-8
references: 22134646
references: Mol Syst Biol. 2008;4:198
references: 18523433
references: PLoS One. 2011;6(9):e24704
references: 21931822
references: Bioinformatics. 2010 Aug 1;26(15):1910-2
references: 20551134
references: Nat Genet. 1999 Jan;21(1):108-10
references: 9916801
references: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2567-72
references: 15701695
references: Annu Rev Genet. 2003;37:283-328
references: 14616063
references: Genome Biol. 2010;11(5):210
references: 20441597
references: PLoS Comput Biol. 2012;8(6):e1002358
references: 22719234
references: Nature. 2012 Jun 13;486(7402):207-14
references: 22699609
references: Nucleic Acids Res. 2010 Jul;38(12):3869-79
references: 20197316
references: Bioinformatics. 2010 Mar 15;26(6):715-21
references: 20130030
references: Mol Biol Evol. 2012 Nov;29(11):3413-25
references: 22752048
references: Sci Transl Med. 2012 May 2;4(132):132ra52
references: 22553250
references: PLoS Biol. 2008 Feb;6(2):e54
references: 18303956
references: PLoS Genet. 2010 Sep 23;6(9):e1001129
references: 20885794
references: ISME J. 2013 Jan;7(1):173-83
references: 22855211
references: BMC Bioinformatics. 2008 Sep 19;9:386
references: 18803844
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D136-43
references: 22139910
references: Genome Res. 2010 Jul;20(7):960-71
references: 20430783
references: Genome Res. 2011 Mar;21(3):494-504
references: 21212162
references: Science. 2011 May 20;332(6032):970-4
references: 21596990
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14
references: 22080510
references: Appl Environ Microbiol. 2006 Jul;72(7):5069-72
references: 16820507
references: Genome Biol. 2012 Jun 14;13(6):R42
references: 22698087
references: Bioinformatics. 2010 Oct 1;26(19):2460-1
references: 20709691
references: PLoS Biol. 2007 Jul;5(7):e156
references: 17579514
references: Science. 1997 Oct 24;278(5338):631-7
references: 9381173
references: Nat Rev Genet. 2012 Mar 13;13(4):260-70
references: 22411464
references: Curr Opin Microbiol. 2007 Oct;10(5):499-503
references: 17933580
references: PLoS Comput Biol. 2012;8(10):e1002743
references: 23133348
references: Ecol Lett. 2006 Jul;9(7):835-45
references: 16796574
references: Adv Med Sci. 2006;51 Suppl 1:81-5
references: 17458065
references: Nat Biotechnol. 2012 Jun 07;30(6):513-20
references: 22678395
references: Proc Biol Sci. 2012 Apr 22;279(1733):1655-64
references: 22090385
references: Genome Res. 2010 Jul;20(7):947-59
references: 20458099
references: Science. 2009 Dec 18;326(5960):1694-7
references: 19892944
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D115-22
references: 22194640
references: Genome Biol. 2012 Apr 16;13(9):R79
references: 23013615
references: Nat Methods. 2010 May;7(5):335-6
references: 20383131
references: ISME J. 2013 Jan;7(1):50-60
references: 22832344
references: Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21390-5
references: 23236140
references: ISME J. 2010 May;4(5):660-72
references: 20182523
references: Bioinformatics. 2004 Jan 22;20(2):289-90
references: 14734327
references: BMC Microbiol. 2012 Nov 01;12:248
references: 23116195
references: Mol Biol Evol. 2005 Aug;22(8):1673-85
references: 16006479