Adams ShmooCon Hack the Genome

8/2/2019 Adams ShmooCon Hack the Genome

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Washington, DC

February 2009

ShmooCon Presentation

Hack the Genome!The Age of Bimolecular Cryptology


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Presentation Agenda

Background and Inspiration

Biology Lesson

DNA as Data

The Toolbox

An Example

Interlude on DNA Computing

How to get started


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Biology Lesson

DNA as Data

The Toolbox

An Example

Interlude on DNA Computing

How to get started


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The Moon Shot of our Generation

Every generation has its signature big

science projects

Ours are the collection and analysis of

the genomes of a whole range of

organisms Being able to do so can provide a

platform for solving some of the key

problems of our age

and

photo: NASA


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Hackers and the genome

The analysis of the genome

data is a deeply collaborative

activity

Never before has a bigscience project been so

open to widespread

participation

Photo by bre pettis: http://www.flickr.com/photos/bre/3230258762/


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Reverse engineering a genome hack the

protocols

Cell-Cell Signaling

Intracellular Pathways

Genome DNA Sequences

Network protocols

Device wiring

Design Drawings


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Collaboration outside of the life sciences

has contributed a lot to theoretical biology

+


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Why? Emerging Diseases.

Better antibiotics for new diseases require

new understanding

Compare the genomes of people with

the microbial genomes

Differences can be exploited with new or

existing pharmaceuticals

wikimedia


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Why? Energy.

Genomes of microorganisms

More efficient production of ethanol,

methane or even butanol

Genomes of algae

Increase in oil production

Improve yield

Produce ethanol or butanol directly?

even engineer for light production?

photo by tochis: http://tochismochis.blogspot.com/


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Why? Cancer.

Finding Better Anti-Cancer Drugs

Comparing the mutations in cancer to

healthy cells

Investigating the outcomes of

treatments

Correlating normally-occurring

differences in genes with risk

wikimedia


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Why? Food.

Improve plant resistance to

drought, pathogens, heat

Improve yield

Adapt for different growingconditions

photo by Scott Kinmartin http://www.scottkinmartin.com/


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Finally Sequenced DNA

http://www.cultivate-int.org/issue8/oriel/index.h


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Why?

We are obtaining biological data at a steadily-increasing rate

an exponential curve steeply tilting to vertical

Converting that data to usable information is a process that is

proceeding, albeit not completely keeping up with its

acquisition Leveraging all that information to create knowledge is an open

challenge, lagging far behind our rate of data collection

Unique opportunities abound in creating an environment that

enables true understanding of this rich sea of data


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Biology Lesson

DNA as Data

The Toolbox

An Example Interlude on DNA Computing

How to get started


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Biology in a nutshell

What follows is the fastest and most incomplete biology lesson

ever.

If you know all of this already, bear with me

If you dont, hold on


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Biological Information:

From: http://www.cerezyme.com/patient/about/cz_pt_about-understanding-1.gif

Cells removed from apatient by a physician

Patient Visit


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Your DNA and you...

Your DNA: Contains the entire plan (more

or less) for you

Compressed, about the same

size as a DVD (3.2e9 bases, in

1 ASCII byte per base) Differs about 1 every thousand

bases from the next person


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DNA contains coded information at many

layers...

http://www.swbic.org/education/comp-bio/images/1c.gihttp://en.wikipedia.org/wiki/Protein_structure
http://www.swbic.org/education/comp-bio/images/1c.gifhttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://www.swbic.org/education/comp-bio/images/1c.gif


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... leading to fully formed and operational

structures
http://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structure


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Biology Lesson

DNA as Data

The Toolbox


How to get started
http://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structure


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How can we turn this biology into a

computable form?

http://bioinformatics.ubc.ca/about/what_is_bioinformatics/
http://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structure


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Like music, DNA is a structured and layered

string of data...

1 aacatacctg ctttatgcac tcaagcagag aagaaatcca caagtactca ccagcctcct61 ggtctgcaga gaagacagaa tcaatatgag cacagcagga aaagtaagca aaaaatatat121 tactgttgat aatatattct cttcaatata acaaataaag gaatacagta ttaataatga181 ataatttaaa atttaaaatt catatctaaa ttagatgatg aataatttaa aattcatatc241 taaattagaa atgatacact ggaatatgat atgcaatata tgctataata tgtaatgtat301 actgaactac agtggaaata agctattcct aaataccttc aaaaagaata tatagaatct361 gtatctattg tctttatttc ctacattaaa taaatttgcc gtaaagtgat agtttattcc421 aagctaatca tgactgattt gtaaacctaa agttagaaaa gtctttaatc agaagctatc481 tttatattaa gaaagcataa tttaaatgtg ttattatttg tattcatatt ttttgtgaac541 acaagaagtc tgacaaaact tttatgagag ggatttgaga agattttgaa atatactttt601 aatcttacta taaaatatct tacaaaatac tcattgatct cacagcatta gaatcatcaa661 ggttaagcaa gacatcacat tcaaattccg tttaaagggg gcccattatg acacaattca721 ggcaatttcc acagaaatct tatggaacag tatctcccct atataaaagt caatatgatc

781 ttacagaaaa ataataatgc aatttgaatc acttattagc actcagaaca caaatatttg841 ttttttcttc tataaattta tacttatttt tcaatgtgtt tacaggtgca cagaaatgca901 tgtggtcatt caatataatc aattgatatt attaattgcc taatttaaaa aaatctgtgc961 aactatttcc agccatttgt tgtgctagga gtgtatcaca caataaaaca cctcactatg

1021 ataattcagt ttaaaggttc tgaggcttac ctttatgctg tgcgacaaaa caggctcatg1081 tcaataagac tggttggaaa tcacatgagt ggcccattgg tactgttctt acaccacttc1141 actttacttt actttcattc attattgatt aatatttaca ttcctcatag aaaataatta1201 gaaaaaagaa aatttaaatt taccatttac taaactcgac ttaaaagaaa taatgagttc1261 atagagcaaa agtataaacc aatcattaat gaaaataata actgatgaaa tagataatcc1321 tcccctcttg agtgcaacat caataactta gctttttgac agcatttcat ttatgtttac1381 ccgtcctgca ttttattttc ctcaatccta aattgtgaca atactaatgt ctatttcata1441 aggtagttgt gagaattcag taaattaata gtgaaaagca cttagaatag tacctggtaa1501 ataaaaataa gtcaataaat attagccact gttattattg ttgctttata actttttgat1561 atttactacc acggagtaca gaaaacgtga ggctacatta attttttcat tcgttttttt

1621 gtttggagat ggagtatctt tctattgccc aggttggagt gcaatggtga tctcggctca1681 ctgcaacctc tgcctcccgg gttcaagtga ttctcctgcc tcagcctcac aagtagctga1741 gtttacaggt acacgccacc atgcttggct aattttagca tttttagtag agacagggtt1801 tcaccatgtt ggtcaggctg gtctccaact cttgacttca ggtgatccgc ccacctcggc1861 ctcccaaagt gctgggatta aagggatggg caactgcacc cggcctgatc tttattctct1921 ggacagccag ctttgagact tcaggaaaat tattcaatca ctgagtcagt tgatcctcaa1981 ttatttcaga tgtagtaaga ccaataattc aatagtactg tcctggtagc atccgtttta2041 ggtttaaaag taattcatat tgtttacagc agcacaattt gcaattgcaa aaatatggaa2101 acttcctaaa tgcccatcaa ccaacgagtg gataaagaga atgtggtata tgtacaccat2161 gagatactac tcagccataa aatggaacaa aataatggcc tttgcagcca cttggatgaa2221 gctgaaggcc attattttaa gtgaagtaac tcaggaatgg aaaaccaaat accatatggt
http://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structure


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Not too different

2800 opt3

2800 A2 41 ldx#65

2802 8A .l txa

2803 20 EE FF jsr&FFEE

2806 E8 inx2807 E0 5B cpx#91

2809 D0 F7 bnel

280B A9 0D lda#13

280D 20 EE FF jsr&FFEE

2810 A9 0A lda#10

2812 4C EE FF jmp&FFEE

ABCDEFGHIJKLMNOPQRSTUVWXYZ

24839539 atg #start (Met)

24839542 gcg Arg

24839545 aac Thr

24839548 gag Asn

24839548 aggt #splice_st. . .

24843113 cagg #splice_end

24843117 gct Ala

. . .

24843113 ata Ile

24843113 taa #end

Alcohol Dehydrogenase
http://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structurehttp://en.wikipedia.org/wiki/Protein_structure


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But the data looks more like this:

CDS 81..1205/gene="ADH5"/gene_synonym="FDH"/gene_synonym="ADHX"/gene_synonym="ADH-3"/gene_synonym="GSNOR"/EC_number="1.1.1.1"

/codon_start=1/product="alcohol dehydrogenase 5, chi polypeptide" /

protein_id="NP_000662.3" /db_xref="GI:71565154" /db_xref="GeneID:128"/db_xref="HGNC:253" /db_xref="HPRD:00064" /db_xref="MIM:103710"/translation="MANEVIKCKAAVAWEAGKPLSIEEIEVAPPKAHEVRIKIIATAVCHTDAYTLSGADPEGCFPVILGHEGAGIVESVGEGVTKLKAGDTVIPLYIPQCGECKFCLNPKTNLCQKIRVTQGKGLMPDGTSRFTCKGKTILHYMGTSTFSEYTVVADISVAKI

DPLAPLDKVCLLGCGISTGYGAAVNTAKLEPGSVCAVFGLGGVGLAVIMGCKVAGASRIIGVDINKDKFARAKEFGATECINPQDFSKPIQEVLIEMTDGGVDYSFECIGNVKVMRAALEACHKGWGVSVVVGVAASGEEIATRPFQLVTGRTWKGTAFGGWKSVESVPKLVSEYMSKKIKVDEFVTHNLSFDEINKAFELMHSGKSIRTVVKI"
http://en.wikipedia.org/wiki/Protein_structurehttp://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=71565153&from=81&to=1205&view=gbwithpartshttp://www.expasy.org/cgi-bin/nicezyme.pl?1.1.1.1http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_000662.3http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=128http://www.genenames.org/data/hgnc_data.php?hgnc_id=253http://www.hprd.org/protein/00064http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103710http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=103710http://www.hprd.org/protein/00064http://www.genenames.org/data/hgnc_data.php?hgnc_id=253http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=128http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=NP_000662.3http://www.expasy.org/cgi-bin/nicezyme.pl?1.1.1.1http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?val=71565153&from=81&to=1205&view=gbwithparts


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And in XML:

71565153NM_000671.3

9606Homo sapiensHomo sapiens alcohol dehydrogenase 5 (class III), chi

polypeptide (ADH5), mRNA2644

GCGCTCGCCACGCCCATGCCTCCGTCGCTGCGCGGCCCACCCCGGATGTCAGCCCCCC

GCGCCGACCAGACTGCAGTTGCTTGGGAGGCTGGAAAGCCTCTCTCCATAGAGGAGATAGAG


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Biology Lesson

DNA as Data

The Toolbox


How to get started


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What about access to tools and data?

You need a couple of things to get started:

Data like DNA sequences, Protein

Structures, and Biological outcomes are

needed for the analysis

Tools for managing, analyzing and

visualizing that data:

Everything from databases to statisticssoftware.

Photo by mandolux: http://www.flickr.com/photos/mandolux/438145176/

http://www.ncbi.nlm.nih.gov/sites/entrez?db=nuccor


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Some sources: Entrez

http://genome.ucsc.edu/cgi-bin/hgTracks?org=huma


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Some sources: UCSC Golden Path

http://www.rcsb.org/pdb/home/home.d


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Some Sources: PDB


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Some tools are extensions of conventional

programming languages:


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Some tools are web-based:


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And some are local applications:


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Even tools for visualizing 3D protein

structures are available
http://www.umass.edu/molvis/workshop/imgs/polyview.htm


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Biology Lesson

DNA as Data

The Toolbox


How to get started


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An example of what you can do: a man-in-

the middle attack on DNA control?

http://en.wikipedia.org/wiki/File:Lac_operon.p

photo by: Ben Stanfield http://flickr.com/photos/acaben/2816139/

D hP l k f i
http://flickr.com/photos/acaben/2816139/http://flickr.com/photos/acaben/2816139/


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DashPat look for common, recurring

words and their placement

ibl id tif i d th t


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possibly identifying words that are

statistically under- and over- represented

Can be associated with genetic

switches upstream of known

genes in a genome

Correlate the identified genes in

a known pathway associated

with metabolism

Next step would be to test the

hypothesis in a laboratory


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Biology Lesson

DNA as Data

The Toolbox


How to get started

W ki th th t I t l d


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Working the other way, too- Interlude on

DNA computing

Translating the problem space to biological


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Translating the problem space to biological

molecules and processes

shows that computing can be done with


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shows that computing can be done with

DNA

Not limited to science alone there are


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o ed o sc e ce a o e e e a e

interesting artistic opportunities, too!

Custom pythonprograms

Rhythm MIDIFile

Melody MIDIFile

Harmony MIDIFile

Retrieve Sequence(ncicb ENTREZ)

RosegardenSequencer

Audacity

Recorder

Python-MIDI


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Biology Lesson

DNA as Data

The Toolbox


How to get started


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Sound interesting? How to get started

Find a buddy a biology expert to help you understand the

underlying science and highlight interesting/important

problems

Take some classes everything from basic biology to

advanced bioinformatics are available online, often by major

players in the field and often free Communicate with your peers there are all kinds of

opportunities to work with others in bioinformatics- from the

conventional (publish and present) to virtual activities like IRC,

forums, social networking, etc.

Stay current with the research many journals are availablefor reading and review, some of the best are open and freely

available


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A sampling of online classes:

MIT OpenCourseware Examples(See: http://ocw.mit.edu/OcwWeb/web/courses/courses/index.htm)

6.092 Bioinformatics and Proteomics

6.895 / 6.095J Computational Biology:

Genomes, Networks, Evolution

6.096 Algorithms for Computational

Biology

Stanford Bioinformatics Online

(See: http://motif.stanford.edu/courses.html/)

Biochem 218 Computational Molecular

Biology

Biochem 238 Computational Proteomics Biochem 228 Computational Genomic

Biology

Some (virtual) places to meet and


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Some (virtual) places to meet and

communicate


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Stay Current with journal articles

PubMed (and freely-available PubMed

Central articles)

Freely-available journals at Public

Library of Science and elsewhere

Your local University library

photo by sifter: http://www.flickr.com/photos/sifter/370775225/


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Now

Get out there and hack the genome!

Adams ShmooCon Hack the Genome

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