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WHY DNA SEQUENCE ANALYSIS OF
THE HUMAN MICROBIOME IS
PRESENTLY A CAUSE FOR DESPAIR,
AND THE AVENUES WE MUST
CONSIDER IN ORDER TO IMPROVE
THE TYPES OF INFORMATION WE
CAN RECOVER TO YIELD
SATISFACTORY TRANSLATION TO
HUMAN HEALTH WITHOUT
INDUCING UNDUE RISK
ENTERCHORUS
3
O for a microbiome, that would produce
The brightest heaven of well-being,
http://www.diapedia.org/type-1-diabetes-mellitus/microbiome-and-type-1-diabetes
4
A colon for a stage, microbes to act
Immune cellsto impair the swelling scene!
Madan R, Jr WA. Immune responses to Clostridium difficile infection. Trends Mol Med. 2012 Nov;18(11):658-66.
https://www.nimml.org/infectious-diseases
5
Then should the coats of science, with their tools,
Assess the DNA; and, with machines,
https://en.wikipedia.org/wiki/Science_education?oldformat=true#mediaviewer/File:Argonne_lab_education.jpg
https://en.wikipedia.org/wiki/DNA#/media/File:A-DNA,_B-DNA_and_Z-DNA.png
https://commons.wikimedia.org/wiki/File:Clostridium_difficile_EM.png
M Derrien, EE Vaughan, CM Plugge & WM de Vos (2004) Akkermansia muciniphila gen. nov., sp. nov., a hunman intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54: 1469-76
http://ibdwatch.com/tag/faecalibacterium-prausnitzii/
http://www.wikiwand.com/en/Apple_IIc
Clostridium difficile
Akkermansia muciniphila
Faecalibacterium
prausnitzii
6
unleashed like hounds, with sequence database
Crouched for employment. But data, and records all,
thetechguysblog.com
Moore’s Law (sorta)
Growth of DNA sequence databases
7
meet flat unraised methods thathave dared
On this unworthy scaffold to bring forth
?
soft
ware
8
So great an insight:can this workflow yield
The vasty fields of bugs? or may we cram
☺
 Day
Abundance
9
Within this paper O, the very knowledge
Thatdid contain the poop of test rodents?
Langille et al. (2014) Microbiome
http://www.nature.com/nature/journal/v420/n6915/fig_tab/420515a_F1.html
Mice
Gut
bacteria
10
O, pardon! sincethe key predictions may
mislead in callousways the function;
Schnoes AM, Brown SD, Dodevski I, Babbitt PC. Annotation error in public
databases: misannotation of molecular function in enzyme superfamilies. PLoS
Comput Biol. 2009 Dec;5(12):e1000605.
11
And let us, sifters of these datasets,
On your particular statisticswork.
http://kiwi.cs.dal.ca/Software/STAMP
12
Suppose within the girdle of this plot
Are now confined two mighty monarchies,
Lawley TD, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile
disease in mice. PLoS Pathog. 2012;8(10):e1002995.
13
but sequence fragments with abutting points
Microbial genomes have beentorn asunder:
http://molbiol-tools.ca/Genomics.htm
DNA sequencing Short sequence fragments
Reassemble Complete genome
(if you’re lucky)
14
Piece out the crucial microbes with our thoughts;
From allten thousand parts derived from man,
15
And make new probiotic treatments;
Think when I speak of yogurt, thatyou taste it
www.webmd.com
https://commons.wikimedia.org/wiki/File:Yogurtland_Yogurt_High_Res.jpg
16
bringing the proud cellsi' the receiving gut;
For penicillin must not intrude,
https://commons.wikimedia.org/wiki/Category:Intestine#/media/File:Blausen_0432_GastroIntestinalSystem.png
https://en.wikipedia.org/wiki/Penicillin
17
fabricate cures from poo; found in feces,
Turning helpful symbionts of many types
http://imgur.com/gallery/yvGCsMx
http://www.typesofeverything.com/types-of-bacteria/
18
Into a little pill: for the which supply,
So let us work on novel therapies;
https://commons.wikimedia.org/wiki/File:Birmingham;_Hospitals_Centre;_an_elderly_patient._Wellcome_L0002291EA.jpg
http://capsuleusa.com/size-0-translucent-capsules/size-0-empty-gelatin-capsules-translucent-coffee-brown-1000-ct
19
with customized communities in play,
www.masslive.com
van Nood Eet al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.
20
aiding the sick,sending disease away.
www.masslive.com
van Nood Eet al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.
93.8% cured
EXIT.
21
With sincerest apologies* to William Shakespeare and
everyone who has ever portrayed Henry the Fifth www.dailymail.co.uk
*Not really a sincere apology

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DCSI presentation 2015

  • 1. WHY DNA SEQUENCE ANALYSIS OF THE HUMAN MICROBIOME IS PRESENTLY A CAUSE FOR DESPAIR, AND THE AVENUES WE MUST CONSIDER IN ORDER TO IMPROVE THE TYPES OF INFORMATION WE CAN RECOVER TO YIELD SATISFACTORY TRANSLATION TO HUMAN HEALTH WITHOUT INDUCING UNDUE RISK
  • 3. 3 O for a microbiome, that would produce The brightest heaven of well-being, http://www.diapedia.org/type-1-diabetes-mellitus/microbiome-and-type-1-diabetes
  • 4. 4 A colon for a stage, microbes to act Immune cellsto impair the swelling scene! Madan R, Jr WA. Immune responses to Clostridium difficile infection. Trends Mol Med. 2012 Nov;18(11):658-66. https://www.nimml.org/infectious-diseases
  • 5. 5 Then should the coats of science, with their tools, Assess the DNA; and, with machines, https://en.wikipedia.org/wiki/Science_education?oldformat=true#mediaviewer/File:Argonne_lab_education.jpg https://en.wikipedia.org/wiki/DNA#/media/File:A-DNA,_B-DNA_and_Z-DNA.png https://commons.wikimedia.org/wiki/File:Clostridium_difficile_EM.png M Derrien, EE Vaughan, CM Plugge & WM de Vos (2004) Akkermansia muciniphila gen. nov., sp. nov., a hunman intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol. 54: 1469-76 http://ibdwatch.com/tag/faecalibacterium-prausnitzii/ http://www.wikiwand.com/en/Apple_IIc Clostridium difficile Akkermansia muciniphila Faecalibacterium prausnitzii
  • 6. 6 unleashed like hounds, with sequence database Crouched for employment. But data, and records all, thetechguysblog.com Moore’s Law (sorta) Growth of DNA sequence databases
  • 7. 7 meet flat unraised methods thathave dared On this unworthy scaffold to bring forth ? soft ware
  • 8. 8 So great an insight:can this workflow yield The vasty fields of bugs? or may we cram ☺  Day Abundance
  • 9. 9 Within this paper O, the very knowledge Thatdid contain the poop of test rodents? Langille et al. (2014) Microbiome http://www.nature.com/nature/journal/v420/n6915/fig_tab/420515a_F1.html Mice Gut bacteria
  • 10. 10 O, pardon! sincethe key predictions may mislead in callousways the function; Schnoes AM, Brown SD, Dodevski I, Babbitt PC. Annotation error in public databases: misannotation of molecular function in enzyme superfamilies. PLoS Comput Biol. 2009 Dec;5(12):e1000605.
  • 11. 11 And let us, sifters of these datasets, On your particular statisticswork. http://kiwi.cs.dal.ca/Software/STAMP
  • 12. 12 Suppose within the girdle of this plot Are now confined two mighty monarchies, Lawley TD, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(10):e1002995.
  • 13. 13 but sequence fragments with abutting points Microbial genomes have beentorn asunder: http://molbiol-tools.ca/Genomics.htm DNA sequencing Short sequence fragments Reassemble Complete genome (if you’re lucky)
  • 14. 14 Piece out the crucial microbes with our thoughts; From allten thousand parts derived from man,
  • 15. 15 And make new probiotic treatments; Think when I speak of yogurt, thatyou taste it www.webmd.com https://commons.wikimedia.org/wiki/File:Yogurtland_Yogurt_High_Res.jpg
  • 16. 16 bringing the proud cellsi' the receiving gut; For penicillin must not intrude, https://commons.wikimedia.org/wiki/Category:Intestine#/media/File:Blausen_0432_GastroIntestinalSystem.png https://en.wikipedia.org/wiki/Penicillin
  • 17. 17 fabricate cures from poo; found in feces, Turning helpful symbionts of many types http://imgur.com/gallery/yvGCsMx http://www.typesofeverything.com/types-of-bacteria/
  • 18. 18 Into a little pill: for the which supply, So let us work on novel therapies; https://commons.wikimedia.org/wiki/File:Birmingham;_Hospitals_Centre;_an_elderly_patient._Wellcome_L0002291EA.jpg http://capsuleusa.com/size-0-translucent-capsules/size-0-empty-gelatin-capsules-translucent-coffee-brown-1000-ct
  • 19. 19 with customized communities in play, www.masslive.com van Nood Eet al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15.
  • 20. 20 aiding the sick,sending disease away. www.masslive.com van Nood Eet al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. 93.8% cured
  • 21. EXIT. 21 With sincerest apologies* to William Shakespeare and everyone who has ever portrayed Henry the Fifth www.dailymail.co.uk *Not really a sincere apology