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The California Institute for Telecommunications and Information Technology
Stability in Health vs. Abrupt Changes in Disease in the Human Gut Microbiome EcologyPresentationArivaleSeattle, WAApril 21, 2016Dr. Larry SmarrDirector, California Institute for Telecommunications and Information TechnologyHarry E. Gruber Professor, Dept. of Computer Science and EngineeringJacobs School of Engineering, UCSDhttp://lsmarr.calit2.net1
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The Knight Lab Uses the Unifrac Metricto Quantitatively Compare Different Microbiome Ecologies
This method, UniFrac, measures the phylogenetic distance between sets of taxa in a phylogenetic tree as the fraction of the branch length of the tree that leads to descendants from either one environment or the other, but not both. UniFrac can be used to determine whether communities are significantly different
A Healthy Persons MicrobiomeIs in a Stable Equilbrium Over TimeBackground is Human Microbiome Project Data
Using Unifrac in Principle Coordinate AnalysisMap Microbiome Ecologies of Individuals to PointsSamples From Multiple Body Sites
Overlay Longitudinal Time Series of Male and Female SubjectDuration 60 DaysTime Points Separated by One DaySampled Oral, Skin, Stool Microbiomes16S Sequencing
MouthStoolVaginaSkinSource: Knight Lab, UCSD
Source: Knight Lab, UCSD
An Unhealthy Persons MicrobiomeCan Abruptly Shift Between Two States With External Influence
Example: Clostridium difficile and Fecal Transplant
Multiple C. diff Patients With a Single Donor
Dramatic Shift Back to Healthy Microbiome in Days
Fecal TransplantsFrom Healthy DonorTo C. Diff PatientsSource: Knight Lab, UCSD
LS Weekly Weight During Period of 16S Microbiome AnalysisAbrupt Change in Weight and in Symptoms at January 1, 2014AntibioticsPrednisoneLialdaUcerisFrequent IBD SymptomsWeight LossFew IBD SymptomsWeight GainSource: Larry Smarr, UCSDBlue Dots weekly average weightRed Dot-Stool Samples Taken
In 2016 We Are Extending My Stool Time Series byCollaborating with the UCSD Knight Lab
Larrys 40 Stool Samples Over 3.5 Years to Robs lab on April 30, 2015
LS Gut Microbiome Time Series by Taxonomy16S Evolution by Family-No Clear Separation at January 2014
Data from Justine Debelius & Jose Navas, Knight Lab, UCSD; Larry Smarr Analysis, January 2016
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LS Gut Microbiome Time Series by Shannon Alpha-DiversityHints at Change Around January 2014Source: Justine Debelius, Knight Lab
Shannon -DiversityPoints represent the average of 10 rarefaction instances at 15,000 sequences/sample.
Error bars are the standard deviation.
Red line is the boxcar moving average over 3 points.PhylogeneticDistanceLS Weight
Time Development Over 3.5 Years of Larry Smarrs Gut Microbiome Ecology:Unifrac Distance of 16S OTUs Transformed into Principle Coordinates
Blue: 1/2012 to 1/2014
Red: 1/2014 to 8/1/2015Movie and Data Analysis by Justine Debelius & Jose Navas, Knight Lab, UCSDUnweighted UniFrac Distance of 16S OTUs was Computed and then Transformed into Principle Coordinates Space Using QIIME. Principle Coordinates were Visualized in Emperor.
Larry Smarr Gut Microbiome Ecology Shifted After Drug Therapy Between Two Time-Stable Equilibriums Correlated to Physical Symptoms
Lialda & Uceris
12/1/13 to 1/1/1412/1/13-1/1/14
Frequent IBD SymptomsWeight Loss
5/1/12 to 12/1/14Blue Balls on Diagram to the Right Few IBD SymptomsWeight Gain
1/1/14 to 1/1/16Red Balls on Diagram to the Right Principal Coordinate Analysis of Microbiome Ecology
PCoA by Justine Debelius and Jose Navas, Knight Lab, UCSDWeight Data from Larry Smarr, Calit2, UCSDAntibioticsPrednisone
1/1/12 to 5/1/125/1/12Weekly Weight (Red Dots Stool Sample)Few IBD SymptomsWeight Gain
1/1/14 to 1/1/16Red Balls on Diagram to the Right
Significantly Different Genus EvolutionDuring LS Time Series
FirmicutesBacteriodetesProteobacteriaActinobacteriaTenericutesAnalysis by Justine Debelius, UCSD
Candidate OTU by PhylaChanges Before and After Jan. 2014Lost before 1/2014Gained after 1/2014Firmicutes3833Bacteriodetes17Proteobacteria12Actinobacteria01Tenerictues21Cyanobacteria11Total4543
Analysis by Justine Debelius, UCSDKruskal-Wallis Test with an FDR q < 0.1.
Tree of all otus with frd_p < 0.1 after Chi-square test.
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To Expand IBD Project the Knight/Smarr Labs Were Awarded ~ 1 CPU-Century Supercomputing TimeSmarr Gut Microbiome Time SeriesFrom 7 Samples Over 1.5 Years To 50 Samples Over 4 Years
IBD Patients: From 5 Crohns Disease and 2 Ulcerative Colitis Patients to ~100 Patients50 Carefully Phenotyped Patients Drawn from Sandborn BioBank43 Metagenomes from the RISK Cohort of Newly Diagnosed IBD patients
New Software Suite from Knight LabRe-annotation of Reference Genomes, Functional / Taxonomic VariationsNovel Compute-Intensive Assembly Algorithms from Pavel Pevzner
8x Compute Resources Over Prior Study
Thanks to Our Great Team!Calit2@UCSD Future Patient TeamJerry SheehanTom DeFanti Joe Keefe John GrahamKevin PatrickMehrdad YazdaniJurgen Schulze Andrew Prudhomme Philip Weber Fred RaabErnesto Ramirez
JCVI TeamKaren Nelson Shibu Yooseph Manolito Torralba
AyasdiDevi RamananPek LumUCSD Metagenomics TeamWeizhong Li Sitao Wu
SDSC TeamMichael Norman Mahidhar Tatineni Robert Sinkovits
UCSD Health Sciences TeamDavid BrennerRob Knight Lab Justine Debelius Jose Navas Gail Ackermann Greg HumphreyWilliam J. Sandborn Lab Elisabeth Evans John Chang Brigid Boland
Dell/R SystemsBrian KucicJohn Thompson