The composition of the complex microbial communities inhabiting the human body has a tremendous influence on human health and disease. New DMA sequencing technologies offer the opportunity to study these communities by directly identifying the genome of individual microbial strains. Ideally, new sequences from metagenomic sampling can be compared to the known, full sequences of individual strains. It is estimated that there are more than 1,000 such reference strain sequences that are required and -600 that are either already determined, or else are in the process of being sequenced. The primary aim of this proposal is to generate reference DMA sequences of the remaining -400 strains to complete this reference catalogue. First, all 400 strains will be sequenced and assembled by shotgun methods. At least 60 will be finished to high quality using established methods and new approaches to convert the majority of the remainder to similarly high quality will be developed. The sequencing will use next-generation methods, based upon platforms developed by 454 Life Sciences, Illumina/Solexa and Applied Biosystems. All of the sequences wiN be annotated by an automated pipeline, and the 60 that are 'finished'will also be manually curated. The sequencing methods will also be applied to a selection of viral and fungal targets. Metagenomic sampling approaches will be tested using existing samples and methods, and these data will be refined by development of new technologies for selective DMA isolation and 16S and WGS sequencing of metagenomic samples, including microarray DMA chip capturing, electrophoretic techniques and cDNA tests. When all technical advances are combined, the cost of sequencing an individual bacterial genome will be less than $1,000.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HG004973-01
Application #
7645310
Study Section
Special Emphasis Panel (ZRG1-GGG-J (52))
Program Officer
Proctor, Lita
Project Start
2009-06-19
Project End
2011-04-30
Budget Start
2009-06-19
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$940,000
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Lloyd-Price, Jason; Mahurkar, Anup; Rahnavard, Gholamali et al. (2017) Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550:61-66
Chu, Derrick M; Ma, Jun; Prince, Amanda L et al. (2017) Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 23:314-326
Chu, Derrick M; Antony, Kathleen M; Ma, Jun et al. (2016) The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med 8:77
Hollister, Emily B; Riehle, Kevin; Luna, Ruth Ann et al. (2015) Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome 3:36
Ma, Jun; Purcell, Heidi; Showalter, Lori et al. (2015) Mitochondrial DNA sequence variation is largely conserved at birth with rare de novo mutations in neonates. Am J Obstet Gynecol 212:530.e1-8
Antony, Kathleen M; Ma, Jun; Mitchell, Kristen B et al. (2015) The preterm placental microbiome varies in association with excess maternal gestational weight gain. Am J Obstet Gynecol 212:653.e1-16
Spinler, Jennifer K; Sontakke, Amrita; Hollister, Emily B et al. (2014) From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillus reuteri have diverse probiotic functions. Genome Biol Evol 6:1772-89
Aagaard, Kjersti; Ma, Jun; Antony, Kathleen M et al. (2014) The placenta harbors a unique microbiome. Sci Transl Med 6:237ra65
Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman et al. (2014) Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis. PLoS One 9:e88645
Kozich, James J; Westcott, Sarah L; Baxter, Nielson T et al. (2013) Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol 79:5112-20

Showing the most recent 10 out of 26 publications