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

Robert Beiko

October 2, 2015

ENTER CHORUS

O for a microbiome, that would produceThe 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 actImmune cells to 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

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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.jpghttps://en.wikipedia.org/wiki/DNA#/media/File:A-DNA,_B-DNA_and_Z-DNA.png

https://commons.wikimedia.org/wiki/File:Clostridium_difficile_EM.pngM 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:

1469-76http://ibdwatch.com/tag/faecalibacterium-prausnitzii/

http://www.wikiwand.com/en/Apple_IIc

Clostridium difficile

Akkermansia muciniphila

Faecalibacterium prausnitzii

unleashed like hounds, with sequence databaseCrouched for employment. But data, and records

all, thetechguysblog.com

Moore’s Law (sorta)

Growth of DNA sequence databases

meet flat unraised methods that have daredOn this unworthy scaffold to bring forth

?soft

ware

So great an insight: can this workflow yieldThe vasty fields of bugs? or may we cram

☺

Day

Abun

danc

e

Within this paper O, the very knowledgeThat did contain the poop of test rodents?

Langille et al. (2014) Microbiomehttp://www.nature.com/nature/journal/v420/n6915/fig_tab/420515a_F1.html

Mice

Gutbacteria

O, pardon! since the key predictions maymislead in callous ways the function;

Schnoes AM, Brown SD, Dodevski I, Babbitt PC. Annotation error in publicdatabases: misannotation of molecular function in enzyme superfamilies. PLoS

Comput Biol. 2009 Dec;5(12):e1000605.

And let us, sifters of these datasets,On your particular statistics work.

http://kiwi.cs.dal.ca/Software/STAMP

Suppose within the girdle of this plotAre 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.

but sequence fragments with abutting pointsMicrobial genomes have been torn asunder:

http://molbiol-tools.ca/Genomics.htm

DNA sequencing Short sequence fragments

Reassemble Complete genome(if you’re lucky)

Piece out the crucial microbes with our thoughts;From all ten thousand parts derived from man,

And make new probiotic treatments;Think when I speak of yogurt, that you taste it

www.webmd.comhttps://commons.wikimedia.org/wiki/File:Yogurtland_Yogurt_High_Res.jpg

bringing the proud cells i' the receiving gut;For penicillin must not intrude,

https://commons.wikimedia.org/wiki/Category:Intestine#/media/File:Blausen_0432_GastroIntestinalSystem.pnghttps://en.wikipedia.org/wiki/Penicillin

☺ ☺☺

fabricate cures from poo; found in feces,Turning helpful symbionts of many types

http://imgur.com/gallery/yvGCsMxhttp://www.typesofeverything.com/types-of-bacteria/

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.jpghttp://capsuleusa.com/size-0-translucent-capsules/size-0-empty-gelatin-capsules-translucent-coffee-brown-1000-ct

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.

aiding the sick, sending disease away.

www.masslive.comvan 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

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EXIT.

With sincerest apologies* to William Shakespeare and everyone who has ever portrayed Henry the Fifth

www.dailymail.co.uk*Not really a sincere apology