DNA...ddRADseq Peterson B. K. et al. (2012) PLoS One 7: e37135 Digenome-seq Kim D et al. (2015) Nat...

transcript

or all you seq...

2b-RAD Wang S et al. (2012) Nat Methods 9:808-8103C Duan Z. et al. (2012) Methods 58: 277-2884-C Zhao Z. et al. (2006) Nat Genet 38: 1341-13475-C Dostie J. et al. (2007) Nat Protoc 2: 988-1002Aba-seq Sun Z. et al. (2013) Cell Rep 3: 567-576ATAC-Seq Buenrostro J. D. et al. (2013) Nat Methods 10:

1213-1218BisChIP-Seq Statham A. L. et al. (2012) Genome Res 22:

1120-1127Bisulfite-seq Berman B. P. et al. (2012) Nat Genet 44: 40-46BLESS Crosetto, N. et al. Nat. Methods 10, 361–365 (2013).Break-seq Hoffman E. A. et al. (2015) Genome Res 25: 402-412BSAS Masser D. R. et al. (2013) Epigenetics Chromatin 6:

33BSPP Deng J. et al. (2009) Nat Biotechnol 27: 353-360BS-Seq Lister R. et al. (2009) Nature 462: 315-322

Bubble-Seq Mesner L. D. et al. (2013) Genome Res 23: 1774-1788

CAB-Seq Lu X. et al. (2013) J Am Chem Soc 135: 9315-9317caMAB-seq Wu H et al. (2016) Nat Protoc 11:1081-100CAP-seq Illingworth R. S. et al. (2010) PLoS Genet 6:

e1001134Capture-C Hughes J. R. et al. (2014) Nat Genet 46: 205-212CATCH-IT Deal R. B. et al. (2010) Science 328: 1161-1164Chem-Seq Anders L. et al. (2014) Nat Biotechnol 32: 92-96Chia-PET Li G. et al. (2010) Genome Biol 11: R22ChIP-BS-seq Brinkman A. B. et al. (2012) Genome Res 22:

1128-1138ChIP-exo Yen K. et al. (2013) Cell 154: 1246-1256ChIPmentation Schmidl C et al. (2015) Nat Methods 12:963-5ChIP-Seq Barski A. et al. (2007) Cell 129: 823-837CPT-seq Amini S. et al. (2014) Nat Genet 46: 1343-1349DamID Vogel M. J. et al. (2007) Nat Protoc 2: 1467-1478

ddRADseq Peterson B. K. et al. (2012) PLoS One 7: e37135Digenome-seq Kim D et al. (2015) Nat Methods 12:237-43DIP-seq Shen L. et al. (2013) Cell 153: 692-706Dnase I SIM Cumbie JS et al. (2015) Plant Methods 11:42DNaseI-Seq Hesselberth J. R. et al. (2009) Nat Methods 6:

283-289DNase-Seq Boyle A. P. et al. (2008) Cell 132: 311-322Drop-ChIP Rotem A et al. (2015) Nat Biotechnol 33:1165-72DR-Seq Dey SS et al. (2015) Nat Biotechnol 33:285-9DSB-seq Baranello L et al. (2014) Int J Mol Sci 15:13111-22Duplex-Seq Schmitt M. W. et al. (2012) Proc Natl Acad Sci U S A

109: 14508-14513EC-seq Parkinson N. J. et al. (2015) Genome Res 25: 226-234EpiRADSeq Schield DR et al. (2016) Methods in Ecology and

Evolution 7:60-69FAIRE-Seq Gaulton K. J. et al. (2010) Nat Genet 42: 255-259fCAB-Seq Song C. X. et al. (2013) Cell 153: 678-691

fC-CET Xia B et al. (2015) Nat Methods 12:1047-50fC-Seal Song C. X. et al. (2013) Cell 153: 678-691FiT-Seq Cejas P et al. (2016) Nat Med G&T-seq Macaulay I. C. et al. (2015) Nat Methods 12: 519-522G4-seq Chambers V. S. et al. (2015) Nat Biotechnol 33:

877-881GUIDE-seq Tsai SQ et al. (2015) Nat Biotechnol 33:187-97HELP-Seq Oda M. et al. (2009) Nucleic Acids Res 37: 3829-3839Hi-C Lieberman-Aiden E. et al. (2009) Science 326:

289-293Histone meth. Barski A. et al. (2007) Cell 129: 823-837HiTS-Flip Nutiu R. et al. (2011) Nat Biotechnol 29: 659-664hMeDIP-seq Xu Y et al. (2011) Mol Cell 42:451-64HT-ChIP Blecher-Gonen R. et al. (2013) Nat Protoc 8: 539-554HTGTS Chiarle, R. et al. (2011) Cell 147, 107–119 HT-SELEX Jolma A. et al. (2010) Genome Res 20: 861-873

HydEn-seq Clausen A. R. et al. (2015) Nat Struct Mol Biol 22: 185-191

hyRAD Suchan T et al. (2016) PLoS One 11:e0151651Ig-Seq Vollmers C. et al. (2013) Proc Natl Acad Sci U S A

110: 13463-13468IMS-MDA Seth-Smith H. M. et al. (2013) Nat Protoc 8:

2404-2412INSeq Goodman AL et al. (2009) Cell Host Microbe 6:279-89JBP1-seq Cui L. et al. (2014) Genomics LAM-HTGTS Hu J et al. (2016) Nat. Protocols 11:853-871MAB-seq Wu H. et al. (2014) Nat Biotechnol MAF Khan TA et al. (2016) Sci Adv 2:e1501371MAINE-Seq Ponts N. et al. (2010) Genome Res 20: 228-238MALBAC Zong C. et al. (2012) Science 338: 1622-1626MBDCap-Seq de Assis S. et al. (2012) Nat Commun 3: 1053MBD-Seq Nair S. S. et al. (2011) Epigenetics 6: 34-44MDA Dean F. B. et al. (2001) Genome Res 11: 1095-1099

MeDIP-Seq Down T. A. et al. (2008) Nat Biotechnol 26: 779-785MethylCap-Seq Brinkman A. B. et al. (2010) Methods 52: 232-236Methyl-seq Brunner A. L. et al. (2009) Genome Res 19:

1044-1056MIDAS Gole J et al. (2013) Nat Biotechnol 31:1126-32MiGS Serre D. et al. (2010) Nucleic Acids Res 38: 391-399MINCE-seq Ramachandran S et al. (2016) Cell 165:580-92Mint-ChIP van Galen P et al. (2016) Mol Cell 61:170-80MIPSTR Carlson K. D. et al. (2015) Genome Res 25: 750-761MIRA Rauch T. A. et al. (2010) Methods 52: 213-217MNase-Seq Schones D. E. et al. (2008) Cell 132: 887-898MPE-seq Ishii H et al. (2015) Proc Natl Acad Sci U S A

112:E3457-65MRE-Seq Maunakea A. K. et al. (2010) Nature 466: 253-257NG Capture-C Davies JOJ et al. (2016) Nat Meth 13:74-80NOME-Seq Han H. et al. (2011) Hum Mol Genet 20: 4299-4310NSCR Kunnev D. et al. (2015) Genome Res 25: 558-569

NS-seq Foulk MS et al. (2015) Genome Res 25:725-35Nucleo-Seq Valouev A. et al. (2011) Nature 474: 516-520nuc-seq Wang Y. et al. (2014) Nature 512: 155-160ORGANIC Zentner G. E. et al. (2013) PLoS Genet 9: e1003317OS-Seq Myllykangas S. et al. (2011) Nat Biotechnol 29:

1024-1027oxBS-Seq Booth M. J. et al. (2012) Science 336: 934-937PAT–ChIP Fanelli M et al. (2011) Nat Protoc 6:1905-19PBAT Miura F. et al. (2012) Nucleic Acids Res 40: e136PB-seq Guertin M. J. et al. (2012) PLoS Genet 8: e1002610PD-Seq Arango D. et al. (2013) Proc Natl Acad Sci U S A 110:

E2153-2162PDZ-Seq Ernst A. et al. (2010) Mol Biosyst 6: 1782-1790PE RAD-Seq Willing E. M. et al. (2011) Bioinformatics 27:

2187-2193ProP-PD Ivarsson Y. et al. (2014) Proc Natl Acad Sci U S A 111:

2542-2547

Pu-seq Daigaku Y. et al. (2015) Nat Struct Mol Biol 22: 192-198

RAD Baird N. A. et al. (2008) PLoS One 3: e3376Rapture Ali OA et al. (2016) Genetics 202:389-400RBBS Meissner A et al. (2008) Nature 454:766-70RC-Seq Baillie J. K. et al. (2011) Nature 479: 534-537RedBS-Seq Booth M. J. et al. (2014) Nat Chem 6: 435-440Repli-Seq Hansen R. S. et al. (2010) Proc Natl Acad Sci U S A

107: 139-144Rep-Seq Benichou J. et al. (2012) Immunology 135: 183-191Ribose-seq Koh K. D. et al. (2015) Nat Methods 12: 251-257RRBS Meissner A. et al. (2008) Nature 454: 766-770RRMAB-seq Neri F. et al. (2015) Cell Rep 10: 674-683Safe-SeqS Kinde I et al. (2011) Proc Natl Acad Sci U S A

108:9530-5scABA-seq Mooijman D et al. (2016) Nat Biotechnol advance

online publication

scATAC-seq Cusanovich DA et al. (2015) Science 348:910-4(Cell index)scATAC-seq Buenrostro J. D. et al. (2015) Nature 523: 486-490(Microfluidics) scBS-seq Smallwood S. A. et al. (2014) Nat Methods 11:

817-820scChIP-seq Rotem A et al. (2015) Nat Biotechnol 33:1165-72scM&T-seq Angermueller C et al. (2016) Nat Methods advance

online publicationscMT-Seq Hu Y et al. (2016) Genome Biol 17:88scRC-Seq Upton KR et al. (2015) Cell 161:228-39scRRBS Guo H. et al. (2015) Nat Protoc 10: 645-659scTrio-seq Hou Y et al. (2016) Cell Res 26:304-19SELEX Jolma A. et al. (2010) Genome Res 20: 861-873SELEX-seq Slattery M. et al. (2011) Cell 147: 1270-1282SLAF-Seq Sun X et al. (2013) PLoS One 8:e58700SMDB Lan F et al. (2016) Nat Commun 7:11784

smMIP Hiatt J. B. et al. (2013) Genome Res 23: 843-854SNES Leung M. L. et al. (2015) Genome Biol 16: 55Sono-Seq Auerbach R. K. et al. (2009) Proc Natl Acad Sci U S A

106: 14926-14931SSB-Seq Baranello L et al. (2014) Int J Mol Sci 15:13111-22TAB-Seq Yu M. et al. (2012) Cell 149: 1368-1380TAmC-Seq Zhang L. et al. (2013) Nat Commun 4: 1517TC-Seq Klein I. A. et al. (2011) Cell 147: 95-106THS-seq Sos BC et al. (2016) Genome Biol 17:20TN-Seq van Opijnen T. et al. (2013) Nat Rev Microbiol 11:

435-442T-WGBS Wang Q. et al. (2013) Nat Protoc 8: 2022-2032UMI-4C Schwartzman O et al. (2016) Nat Methods advance

online publicationWGBS Lister R. et al. (2009) Nature 462: 315-322X-ChIP-seq Skene P. J. et al. (2014) Elife 3: e02042

References

TruSeq RNA

AAAAA mRNA

T T T T TAAAAA polyA select

Fragment

Illumina, Inc. • 5200 Illumina Way, San Diego, CA 92122 USA • 1.800.809.4566 toll-free • 1.858.202.4566 tel • techsupport@illumina.com • illumina.com

FOR RESEARCH USE ONLY

© 2015 Illumina, Inc. All rights reserved.Illumina, HiSeq, MiSeq, MiniSeq, Nextera, NextSeq, TruSeq, the pumpkin orange color, and the Genetic Energy streaming bases design are trademarks or registered trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners. Pub. No. 373-2016-005 Current as of 10 November 2016

MoleculoSheared genomic DNA

End repair

Adapter ligation

Prepared fragments

Index 2

Index 1

Index 2

Index 1

Transposase

Tagmentation

~600bpP5

Index 2

Index 1

P5 P7P5 P7P5 P7

Generate clonal poolsAmplify

Add indices

Pool and purify

Sequencing by Synthesis

TruSeq PCR Free

Double-stranded DNA

FractionateSize select

A-overhang

End repairPhosphorylate

IndexT

Index Adaptor ligation

P5P7Index

Add Adaptors

Product ready for cluster generation

TruSeq NanoDouble-stranded DNA

FractionateSize select

A-overhang

End repairPhosphorylate

Index 1Index 2

Index 2Index 1

Adaptor ligation

Denature and amplify

Add Adaptors

Index 1Index 2

Index 2Index 1

P5 P7Index 1Index 2

Double-stranded DNA

TruSeq Custom Amplicon

Add custom probes

Region of interest

Double-stranded DNADouble-stranded DNA

Add custom probes

Extension and ligation

Add sequencing primers

Index 2Index 1

Index 1P7

Index 2P5

Custom Probe 1

Custom Probe 2

TruSeq Small RNA

3’5’ Small RNA fragment

Ligate adaptors

Add primer

Reverse transcription

5’ Adapter 3’ Adapter

Index 1

P5 P7Index

TruSeq RNA Stranded5’ 3’ RNA

Random primer

cDNACreate cDNA

Create second strand cDNA

dUTP + dCTP + dATP + dGTP

dT TP + dCTP + dATP + dGTP

End repairPhosphorylateA-overhang

Adaptor ligation

P5 P7Index 1Index 2

U U U UUUUUUUUSense strand

PU U U UUUUUUUSense strand

Index 1

P5Index 2

U U U UUUUUUU Index 2

Index 1

Sense strand

P5P7U U U UUUUUUU

Sense strand Block polymerase

Nextera Library Preparation

Transposase

~300bp

Tagmentation

Ampli�cation

P5 P7Index 1Index 2

Index 2

Index 1

Nextera Mate Pair

Adaptor ligation

Isolate biotinylatedfragment

Transposase

Tagmentation

Circularize

R R R RBiotinylated junction adapter

Fragment

AATTCGC

Synthesize second strand

The second read is sequenced

Sequence Index2

AATTCGC

Deblock P5 primer and add unlabeled bases

Read 2 primer

The forward-strand is cleaved and washed away

AATTCGC

Adapter hybrid-izes to flowcell

Reverse strand syntesis

Reverse strand

Forward strand

Remove forward strand

Fold over and hybridize to second primer

Synthesize second strand

The reverse strand is cleaved and washed away

With each cycle, four fluores-cently tagged nucleotides compete for addition to the growing chain. Only one is incorporated based on the sequence of the template.

The read product is washed away

Thousands of molecules are amplified in parallel

Reverse strand

Forward strand

Bridge amplification

Sequence primer

Fold over and hybridize to first primer

Sequence Index1

Index 1 primer

The read product is washed away

CH3O CH3

Nextera Rapid Capture

Target

TargetP5 P7

Index 1Index 2 Product ready for cluster generation

Denatured and pooled fragments from Nextera library

Capture on magnetic beads

Hybridize probes to targets

Biotinylated target probe

TruSeq RNA Access

Target

TargetP5 P7

Index 1Index 2 Product ready for cluster generation

Pool stranded RNA-Seq libraries

Biotinylated target probe

Hybridize probes to targets

Capture on streptavidin magnetic beads

Random hexam-er

First and second strand synthesis

TruSeq Targeted RNA ExpressionTarget

ULSO DLSO

Total RNA

Hybridization

Index 1

5’ P

Index 2

Target Index 1Index 2 Product ready for cluster generation

Add custom primers

Extension-Ligation

Biotin

This poster was compiled by the Illumina Scienti�c A�airs. Additional information, the latest version of the poster, and a comprehensive list of *seq methods, are available at http://www.illumina.com/libraryprepmethods. Please contact Scienti�c A�airs with any questions, comments, or suggestions.

Display methods on mobile device

CH3O CH3

Display methods on mobile device

DNA Low-Level Detection

DNA Rearrangements and Markers

Duplex-Seq α βVery rare mutation

Duplex sequencing detects rare mutations by sequencing and aligning both strands of the DNA

A mutation occurs on both strands

12 random base index

True variantRandom error

Ligate and PCR Rare variantSequence Create single strand consensus sequence from every unique molecular tag

ConsensusCreate duplex sequences based on molecular tags and sequencing primers

Add adaptors

Ig-seqRep-SeqMAF

CDR3 junction region V D J Constant

DNADNA sequencing of immunoglobulin genes (Ig-seq), repertoire sequencing (Rep-Seq), and molecular ampli�cation �ngerprinting (MAF)

Extracted RNA Reverse transcription8N UID

8N UID

Second strand synthesis PCR Purify

CpG island

CAP-seqDNACXXC a�nity puri�cation plus

deep sequencing (CAP-seq)CXXC bound to nickel-charged sepharose beads

Hybridize to sepharose column

Methylated CpG

Unmethylated CpG

CXXC CXXCX

Elute unmethylated CpG enriched fragments

TC-SeqAID-dependent rearrangement

Infect I-Sel Puri�cation

I-SceI site+AID

-AID AA

DNAGenomic DNATC-Seq: translocation capture sequencing

Sonicate, blunt and A-tail

Ligate linkersCut I-Scel

Semi-nested PCRLinker cleavage

RC-Seq

Genomic DNA Fractionate DNA fragments

Hybridize

Read2Transposon sites

Sequenced fragment

Reference sequence Align

Novel retrotrans-position events

Retrotransposon binding sites Known

retrotrans-poson

Novel retrotransposition events

Microarray with transposon binding sites

RC-Seq: Retrotransposon capture sequencing

TN-SeqINSeq

Transposon Transposon

MmeIMmeI digestion Add adapters

PCR and sequenceTransposon sequencing (TN-Seq) and insertion sequencing (INSeq)

Inverted MmeI recognition site

MmeI recognition site Transposon

insertion sites

MALBACGenome

Hybridize primers PCR

27-bp common sequence8 random nucleotides

Partial amplicons

Template

Denature

Hybridize primers Synthesis

Multiple annealing and looping-based ampli�cation cycles (MALBAC)

Cycles of quasilinear ampli�cation

Looped full amplicons

Bst DNA polymerase

OS-Seq Gene

Target sequence

Adaptor sequence

Flow cell

Sequencing Primers

Target sequence Single adaptor library

Hybridize Hybridize

SequenceOligonucleotide-selective sequencing (OS-Seq) captures and sequence gene targets on the �ow cell

Create target-speci�c oligos Extend and Denature

Extend and Denature

Sequence reads 1 and 2

Fragment and add single adaptors

CPT-Seq

Divide sample into 96 reactions

Dilute and divide into 96 reactions

SDS PCR DNAIndexed transpo-some reactions

EDTAPool

Contiguity-preserving transposition sequenc-ing (CPT-seq)

Genome

Indexed PCR primers

EC-seqV(D)J antigen receptor region

Excision circle sequencing (EC-seq)

Lymphocyte-speci�c recombination activat-ing gene (RAG) recombinase, bound genome

V1 V2 V3 J5 J4 J3 J2 J1 V1 V2 V3 J5 J4 J3 J2 J1

J3 J2 J1V1V2

Synapsis, cleavage and coding end hairpin formation

Resolved genomic coding junction

Liberated excision circle with resolved signal junction

Align read pairs to reference genome

V1 V2 J3 J2 J1

V3 J5J4

V1 V2 V3 J5 J4 J3 J2 J1

HydEn-seqGenome Ribonucleotides

Hydrolytic end sequencing (HydEn-seq) to reveal replicase- and strand-speci�c patterns of ribonucleotides in the genome

Alkaline hydrolysis (KOH)

Phosphorylation (T4 PNK 3-phosphatase minus)

Ligate oligo with 5’-amino- terminated C6 spacer

Add sequencing primers, PCR and sequence

Map locations on the genome

5’ 3’3’ 5’

R R5’HO 5’P-O

2’,3’-cyclic phosphate R R

Genomic DNA

GenesmMIP

Copy target sequence Exonuclease Corrected sequence

Align fragments from every unique molecular tag

Sample indexRead1

True variant

Random errorSingle Molecule Molecular Inversion Probes (smMIPs) for detecting low frequency targets

PCR ampli�cation

Degenerate molecular tag

Targeted STR

Short tandem repeat (STR)MIPSTRCopy target STR Amplify and sequenceTargeted capture of STR

loci by smMIPs (MIPSTR)

Degenerate molecular tag Strain I

Strain IIStrain I

Strain INatural variation between individuals Somatic variation within an individual

G4-seqPotential G-quadruplexGenome

Target sequence

K+ or PDS

Determine the location of potential G-quadruplexes in DNA (G4-seq)

Hibridize sequencing primer

Read reference sequence

Denature and remove read fragment

Add K+ or PDS to stabilize G4 regions

Compare sequence reads 1 and 2

Fragment and create library on �ow cell

Sequencing Primer

Read stabilized squence

Polymerase stalls

nuc-seqSNES

Cell 1

Cell 2

Cell 3

Cell sorting from G2/M distribution

Lyse cell NucleusSingle G2/M nucleus sequencing of cells in S phase (nuc-seq). Single nucleus exome sequencing (SNES)

Single cell genome

Phi 29 Limited ampli�cation S1 nucleaseSynthesis DNA

Ribose-seqGenome with ribonucleotides

Detect ribonucleotides embedded in DNA (Ribose-seq)

Fragmented genomic DNA

DNA for sequencing

dA tailing Adaptor ligation Alkali treatment Self-ligation byAtRNL

Degradation oflinear ssDNA

Remove 2’-phos-phate and PCR

R5’ P

P 5’

R5’ P

P 5’A

AmA TA Am

Am2’P 2’P

Epigenetics

Methylated DNA

RRBSscRRBS Reduced representation bisul�te

sequencing (RRBS-Seq). Single cell RRBS (scRRBS)

Methylated regions

Methylated adapter

End repair and ligation

Bisul�te conversion

Converted fragments PCRPCRMspI digestion

PBATPost-bisul�te adaptortagging (PBAT)

Methylated DNA Capture �rst strand on Streptavi-din coated magnetic beads

Second random priming

Streptavidin

BiotinAdaptor

First random priming

AdaptorRandom primer 2

Generate second strand DNA with adaptorsElution

BS-SeqBisulfite-seqWGBS

DNAShear DNAMethylated DNA Bisul�te conversionBisul�te conversion of genomic DNA (bs-Seq) or whole-genome bisul�te sequencing (WGBS)

C GTCT

C GTUT

Bisul�te

C GTTT

BSPPBisul�te sequencing with padlock probes (BSPP)

CpG island Bisul�te conversion

Bisu�te-converted DNA

HybridizePadlock probe

End repair and adaptor ligation

Extension and ligation

Exonuclease digestion

P1 P2H1 H2

AluI MmeIMmeI

PCR DNA with adaptors

EpiGnomeTM HELP-Seq DNAMethylated DNA Bisul�te conversionBisul�te conversion of genomic DNA without

shearing. HpaII tiny fragment enrichment by ligation-mediated PCR (HELP-Seq)

C GTCT

C GTUT

Bisul�te

C GTTT

Converted single-stranded fragments

Random primingDNA synthesis

3’ tagging PCR

Random primer 1

Methylated DNA Bisul�te conversion

Random primer 2scBS-seqSequenceSingle-cell bisul�te

sequencing (scBSBS-seq)Align fragments from every unique molecular tag

Isolated single cell

Lyse First random priming

Second random priming

Repeat 4 times

PCRExtend

Adaptor AdaptorExo I and purify

Protein-Protein Interactions

DNA-Protein Interactions

ATAC-Seq Fragmented and primed DNAAssay for transposase accessible

chromatin (ATAC-Seq)Tn5 TransposomeOpen DNA DNA puri�cation

Ampli�cationInsert in regions of open chromatin

MAINE-SeqMNase-SeqNucleo-Seq Open chromatin Isolate trimmed complexesMNase digestion DNA extraction DNAMNase-assisted isolation of nucleosomes (MAINE-Seq).

Also Micrococcal nuclease sequencing (MNase-Seq)

FAIRE-seqSono-Seq

DNAOpen DNA Formaldehyde-assisted isolation of regula-tory elements (FAIRE-Seq) and sonication of cross-linked chromatin (Sono-Seq)

Crosslink protein and DNA with formalin Sonicate Phenol extract and purify DNA from the aquous phase

NOMe-SeqOpen DNA Nucleosome Occupancy Methylome-

Sequencing (NOMe-Seq), a single-molecule nucleosome positioning assay

Bisul�te conver-sion BS-Seq

CpG dinucleotides Methylated CpG

GpC methyltransferase (M.CviPI) and S-Adenosyl methionine (SAM)

Protected methylated

Protected unmethylated

Unprotected methylated

Unprotected unmethylated

Protected Protected

M.CviPI

Control

DNADNA extraction

Enrich DNA fragments

Add biotinylated compound

Crosslink

Chem-seq

Identify sites bound by small chemical molecules (Chem-seq)

DNA-protein complex with putative drug binding site

in vivo

in vitro

Streptavidin

Add biotinylated compound

Harvest cells and fragment DNA

HiTS-FLIPTarget sequence

Scan �owcellHybridizeHigh-throughput sequencing: �uorescent ligand interaction pro�ling (HiTS-FLIP)

Protein binding site

Prepare sequencing libraries and sequence �rst strandRemove second strand DNA

Flowcell

Hybridize primer

Synthesize second strand with unmodi-�ed nucleotides

Add �uorescent-ly labeled ligand

Elute with increas-ing stringency

Binding siteKlenow

ChIP-SeqChIP-exoHT-ChIPMint-ChIP

Exonuclease digestion Immunoprecipitate DNADNA-protein complex DNA extraction

Crosslink proteins and DNA Sample fragmentationChromatin immune precipitation (ChIP-Seq), High-throughput chromatin immunoprecipi-tation (HT-ChIP))

PB-seqDNADNA-protein complex DNA

extractionHybridize with DNA-binding protein

Isolate protein-bound DNA

Purify DNA Shear DNAProtein/DNA binding (PB–seq), to determine the binding energy landscape

ProP-PDPDZ-Seq

Hybridize

Proteomic peptide-phage display (ProP-PD) to identify short linear motif (SLiM) interac-tions or PDZ domains (PDZ-Seq)

Protein target

Identify C-terminal sequences

Create oligo library

Construct phage display library

Bait proteins immobi-lized on 96-well plate

Select phages against baits

Peptide counts

Isolate and sequence

CATCH-ITMNase digestion DNACovalent attachment of tags to

capture histones and identify turnover (CATCH-IT)

Isolate nucei

Cycloaddition reaction

Remove of H2A–H2B dimersand non-histone proteins

Cells starved ofmethionine

DNA extraction

Add methionine analogue l-azidohomoalanine (AHA)

Biotin

Streptavidin

ORGANICMNase digestion DNAOccupied regions of genomes from

a�nity-puri�ed naturally isolated chromatin (ORGANIC)

Isolate nuceiCell Isolated chromatin Soluble extract Immunoprecipitate and DNA extraction

X-ChIPMNase digestion DNAHigh resolution of mapping of in vivo

chromatin associated proteins (X-ChIP)Crosslink cells in vivo

Lyse cells Cross-linked chromatin Sonicate Soluble extract

Immunoprecipitate and DNA extraction

Chia-PET

Sample fragmentation Immunoprecipitate Ligation Restriction enzyme digestion DNAChromatin interaction analysis by paired-end tag sequencing (ChIA-PET)

LigationCrosslink proteins and DNA Sample fragmentation DNARestriction digest Self-circularization and Reverse PCR

Chromatin conformation capture circular (4-C)

LigationCrosslink proteins and DNA Sample fragmentation LMA: Ligation-mediated ampli�cation DNA

Chromatin conformation capture carbon copy (5-C)

DNA-protein complex Exonuclease digestion Immunoprecipitate DNADNA extractionCrosslink proteins and DNA

Sample fragmentation

Histone methylation

ChIP-Seq of methylated histones (Histone methylation)

DNA adenine methyltransferase interaction detection (DamID)

DNA-protein interaction

Create fusion protein

Align sequences and determine di�erentially digested sites

Split sample DpnI digestion Unmethylated GATCs are cut by DpnII

Adaptor ligation

Non-targeted methylation

Speci�c and non-targeted methylation

DNA adeninemethyltransferase (DAM)

Protein of interestDAM

Fusion protein DpnII PCRDpnI

SELEXSELEX-seqHT-SELEX

Binding site

High-throughput systematic evolution of ligands by exponential enrichment (HT-SELEX)

Target sequence

Transcription factor binding siteDNA binding regionLuciferaseStreptavidin binding peptide

pD40htSELEX

Expression vectorLigand

Forward sequencing adaptorSequencing primerBarcode to identify sample14N with all possible combinationsReverse sequencing adaptor

Fusion protein immobilized in well

Matching ligand binds

Wash and elute

Recovered matching ligand

PCR and Sequence

LuciferaseFusion protein

Pu-seq ROrigin of replication

DNAPolymerase usage sequencing (Pu-seq)

Klenow reaction(+ random primer, dATP, dGTP,dCTP, dUTP)

Attach adaptors

Uracil DNA glycosylase-and DNA lyase (USER)

Alkali treatment

5’ 3’3’ 5’ U U U

PCR and purify

Index 1Index 2

Break-seq Breakage at replication fork

DNADouble-stranded breaklabeling to map chromosome breaks (Break-seq)

End-repair with dGTP, dCTP, dTTP, and biotinylated-dATP

Elution and fragmentation

Attach adaptors

DNA trapped in agarose gel

Break5’ 3’3’ 5’

PCR and purify

Index 1Index 2

Streptavidin magnetic bead pull down

5’ 3’3’ 5’

Yellow highlights indicate the target of the protocol

PD-SeqWash

Hybridize

PD-Seq identi�es candidate cellular targets for proteins

Protein target

Pyridine

Polyethylene glycol linker added

Immobilized protein

RNA from cells

NH2 NH2K2CO3

Create phage display cDNA library

Repeat cycle three times

PCR phage insert

DNAProtein-protein interaction

MeDIP-SeqDIP-seq

Extract DNA FractionateDenature

ImmunoprecipitateMethylated DNAMethylated DNA Immunoprecipitation (MeDIP-Seq), DNA immunoprecipitation followed by high throughput sequencing (DIP-seq))

DNADNA puri�cation

hMeDIP-Seq

Extract DNA FractionateDenature

ImmunoprecipitateHydroxymethylated DNA

Hydroxymethylated DNA immunopre-cipitation combined with next genera-tion DNA sequencing (hMeDIP-seq)

T-WGBSDNATagmentation-based

whole-genome bisul�te sequencing (T-WGBS)

Methylated DNA TagmentationTransposome withmethylated adaptor

Displaced oligo

Oligo withmethylated adaptor

Displace oligoHybridize methylated adaptor and gap repair

PCRBisul�te conversion

TAmC-Seq5cmC

Tet-assisted 5-methylcytosine sequencing (TAmC-Seq)

5mc residue βGT

Glucosylation OxidationGCC CT

5hmC 5mC

GCC CT

g5hmC 5mCTET

GCC CT

DNAβGT-catalyzed UDP-6-N3 glucosylation

Biotinylation Streptavidin pulldownand DTT cleavage

GCC CT

g5hmC BiotinN3S-S

GCC CT

fC-Seal5fc residue

Blocked 5hmC residue

5hmC residue

A 5-formylcytosine-selective chemical labeling (fC-Seal) approach for genome-wide pro�ling of 5fC

βGT-catalyzed glucosylation

βGT-catalyzed UDP-6-N3 glucosylation

BiotinylationConvert 5fc to 5hmc

Streptavidin pulldownand DTT cleavage

5fc5mC

CC C CC CC C CC

CC C CC

BiotinN3S-S

CC C CC

oxBS-SeqOxidative bisul�te sequencing (oxBS-Seq) to map 5-methylcytosine and 5-hydroxymethylcytosine

DNAKRuO4

5hmc residue ControlBisul�te treatmentPCR ampli�cation

Bisul�te treatmentPCR ampli�cation

C TCT T

TCT TT

5fc5mC

C C CCC

MAB-seqM.SssI methylase-assisted bisul�te sequencing (MAB-seq) to map 5fC/5caC

DNAM.SssI

5fC/5caC residues ControlC TCT T

C TCC T

5fc5mC5hmC

5fc5mC

CCC CC

RRMAB-seq Reduced representation M.SssI methylase-assisted bisul�te sequencing (RRMAB-seq)

DNAM.SssI Digest with MspI

Add methylated adapters

5fC/5caC residues ControlC TCT T

C TCC T

5fc5mC

CCC CC

5fc5mC

C TCT T

RedBS-SeqcaMAB-seq Reduced bisul�te sequencing

(redBS-Seq), to map 5-formylcyto-sine (5fC) in DNA

DNANaBH4

5fc residue Control

CCT TC

5fc5mC5hmC

5fc5mC

C CC C C

C TCT T

fCAB-Seq5fC chemically assisted bisul�te sequencing (fCAB-seq) method for the base-resolution detection of 5fC

DNAO-ethylhydroxylamine (EtONH2)

5fc residue ControlBlocked

CCT TC

5fc5mC5hmC

5fc5mC

C CC C C

C TT T TTAB-SeqTET-assisted bisul�te sequencing, (TAB-Seq) to map 5-hydroxymethylcytosine

5hmc residue βGT

Glucosylation Oxidation

TET Bisul�te treatmentPCR ampli�cation

5fc5mC 5gmC

CC C CC

JBP1-seqDNAJ-binding protein 1 sequencing

(JBP1-seq), for genome-wide pro�ling of 5-hydroxy-methylcytosine (5hmC)

TagmentationTransposomes Glucosylated 5-hmC PCRJBP1-magnetic bead pull down

5hmc residues

T4-βGTHydroxy-methyl-ated DNA

Aba-seqDNAAbaSI coupled with sequencing

(Aba-seq) to map high-resolution hydroxymethylome (5hmC)

Glucosylated 5-hmC Streptavidin magnetic bead pull down

5hmc residues

AbaSI Biotinylated primers

Ligate Fragment

CAB-SeqSequence

5caC residue

Chemical modi�cation-assisted bisul�te sequencing (CAB-Seq) for 5caC detection

1-ethyl-3-[3-dimethylamino-propyl]-car-bodiimide hydrochloride (EDC) chemistry

Streptavidin pulldownand DTT cleavage

Nu S-S

Linker Bisul�te treatmentPCR ampli�cation

5fc5mC o-acylisourea5hmC

5fc5mC BiotinS-S5hmC

CC C5caC

5fc5mCCCT T T

C CC TT

Control5hmC

5fc5mC

CCC CCS5caC

Extract DNA Fractionate Elute with increasingsalt concentration

Methylated DNA

Methyl-CpG binding domain-based capture and sequencing (MBDCap-seq). Capture of methylated DNA using the MBD domain of MeCP2 (Methyl-Cap-Seq). MBD-isolated Genome Sequencing (MiGS)

Capture biotinylated MBD on Streptavidin coated magnetic beads

MBDStreptavidinBiotin

MBDCap-seqMethyl-Cap-seqMBD-SeqMiGS

MIRAMethylated-CpG island recovery assay (MIRA)

5mc CpG island

DNA puri�cationPCR ampli�cation

GC G GCGC G

MBD2B/MBD3L1 protein complex

Isolate on glutathione-coated beads

Fractionate

CGCGCGC G

Methyl-SeqMRE-Seq Methyl-seq and MRE-Seq use

methyl-sensitive enzymes to identify methylation patterns

Methylated sites in the genome

GGC CGGC C

Sequence Align sequences and determine undigested sites

Split sample Identi�ed methylation site

Restriction enzyme digest

BSASDNABisul�te amplicon

sequencing (BSAS)Methylated DNA TagmentationTransposome with

adaptorAmpliconsPCR with primers speci�c for

bisul�te converted DNABisul�te conversion

Bisu�te-con-verted DNA

5-Methyl Cytosine

Cytosine

5-formylcytosine (5fC)R

5-carboxylcytosine (5caC)R

5-hydroxymethylcytosine (5hmc)

Cytosine 5-Methyl Cytosine

5-Methyl Cytosine

Uracil

Glucosylated 5hmc

Uridine diphosphate glucose (UDP-Glu)

N3-5GMC

Pyridostatin (PDS)

NH NHO

Pyridine

Bubble-Seq

Libraries of restriction fragments that contain replication initiation sites (bubbles) in vivo

Bubble-containing fragment

Restriction digest

Run gelCast fragments in trapping gel

Recover bubble-con-taining plug

DNA extraction Add sequencing primers

2b-RADGenome BsaXI restriction sites

Restriction-site associated DNA marker generation (RAD) with type IIB restriction endonucleases (2b-RAD)

Restriction digestion with type IIB restriction endonucleases e.g. BsaXI

Add restriction-site-speci�c adapters

Amplify Amplify DNAAdd sample-speci�c adapters

RADPE RAD-Seq

Genome Restriction sites

Restriction-site associated DNA marker generation (RAD)

Restriction digestion

Shear and size select

Add barcoded adapters Add P2 adapter

Amplify DNA

Genome DNA and mRNA sequencing (DR-Seq)

DR-SeqAA(A)n

Single cell RNA

AA(A)n

Single cell

RT with barcoded primerLyse cell Ad-2 primer

Split samples

Quasilinear ampli�cation

SequencegDNA ampli�cation

cDNA ampli�cationT T T T T T T T T TAAAAAAA

PCR and Remove adaptors

2nd strand synthesis

SLAF-seq Genome Restriction sites

Speci�c locus ampli�ed fragment sequenc-ing (SLAF-seq) for large scale genotyping

Digest with MseI Add MseI adaptors

PCRPCR with barcoded MseI primer

DNAAdd sequencing adaptors

Digest with AluI Purify and pool

Genome and transcriptome sequencing from a single cell (G&T-seq)

G&T-seq

Align RNA and genome

AA(A)n

Single cell RNA

AA(A)n

Cell suspension

Isolate single cell

Separate the DNA and the RNALyse cell Sequence

T T T T T T T T T TAAAAAAA

Streptavidin magnetic bead with mRNA capture primer

T T T T T T T T T TAAAAAAA On-bead transcriptome

ampli�cation with Smart-seq2Whole genome ampli�cation with MDA

Methylome and transcrip-tome sequencing from a single cell (scM&T-seq)

scM&T-seq

Align RNA and methylome

AA(A)n

Single cell RNA

AA(A)n

Cell suspension

Isolate single cell

Streptavidin magnetic bead with mRNA capture primerStreptavidin magnetic bead with mRNA capture primer

ampli�cation with Smart-seq2Whole genome bisul�te sequencing with scBS-seq

Methylome and transcrip-tome sequencing from a single cell (scMT-seq)

scMT-seq

Align RNA and methylome

AA(A)n

Single cell RNA

AA(A)n

Cell suspension

Isolate single cell

Streptavidin magnetic bead with mRNA capture primerStreptavidin magnetic bead with mRNA capture primer

ampli�cation with Smart-seq2Whole genome ampli�cation with RRBS

Rapture Genome Restriction sites

Restriction-site associated DNA marker generation (RAD) capture (Rapture)

Digest with restriction enzyme

Restriction enzyme digest

Add well-speci�c barcodes

Plate 1

DNAHybridize Biotinylatedcapture bait

Pool wells and shear

Library prep with plate barcodes

Well 1Well 2

Streptavidin pull down

Plate 2

Hi-C3-CCapture-C

LigationCrosslink proteins and DNA Sample fragmentation PCR amplify ligated junctions DNAChromatin conformation capture (3-C, Hi-C and Capture-C)

NG Cap-ture-C

LigationFormaldehyde �xation Restriction enzyme digestion

De-crosslink and extract DNA

Sonicate to 200 bp fragments

DNAPCRNext-generation Capture-C (NG Capture-C)

Add indexed sequencing adaptors

Hybridize biotinylatedcapture bait

LAM-HTGTSDNALinear ampli�cation-mediated

high-throughput genome-wide sequencing (LAM-HTGTS)

Fragmentation by sonication

Tagged PCREnzyme blocking

Nested PCR

Purify

Breakage in genome

Adaptor ligationLAM-PCR with biotinilated primer

NNNNNNNN

HTGTSDNALinear ampli�cation-mediated

high-throughput genome-wide sequencing (HTGTS)

Fragmentation by sonication

Tagged PCRNested PCR

Purify

Breakage in genome

End repair 3’ A addition Adaptor ligation and PCR

ChIPmenta-tion

Fragmented and primed

DNAChromatin immunoprecipitation with sequencing library preparation by Tn5 transposase (ChIPmentation)

Chromatin immunoprecipitationChromatin DNA puri�cationAmpli�cation

Adaptor insertionTn5 Transposome

DNaseI-SIM

DNase I digestion Terminate DNase I digestion

DNA extraction

DNADnase I simpli�ed in-nucleus method (Dnase I SIM) for plants

Cells Lyse and centrifuge

Sort nuclei

Supernatant

Nuclei

Nucleus

Polish ends

fC-CET5fc residue

5fC based on selective chemical labeling of 5fC and subsequent C-to-T transition during PCR

5fc5mC N3

CC C CC

BiotinN3

CC C CC

CC C CC CC C CT

DBCO-S-S-PEG3-biotinAzido 1,3-indandione (AI)

Pulldown, NaOH and DTT

Adaptor ligation and PCR

Purify

DNase-SeqDNaseI-Seq

Active chromatin Isolate trimmed complexesDNase I digestion DNA extraction DNADNase I hypersensitive sites sequencing (DNase-Seq, DNaseI-Seq)

MPE-seq

Active chromatin Isolated nuclei Add bathophenanthrolineMPE digestion DNA extraction DNAMethidiumpropyl-EDTA sequencing (MPE-seq)

Methidiumpro-pyl-EDTA (MPE)

NH2H2N

Single-cell triple omics sequencing (scTrio-seq)

scTrio-seqAA(A)n

Single cell RNA

DNA methylation

Cell suspension

Isolate single cell

Lyse and centrifuge

Supernatant

Nucleus

AA(A)nRNA

Add carrier RNA

AA(A)nT T (T)ncDNA synthesis PCR and sequenceAdd poly A with TDTHybridize oligo

AA(A)n

DNAAdd sequencing adaptors PCR and sequence

Align sequencesMethylated regions

Methylated adapter

End repair and ligation

Converted fragments

MspI digestion

PCR and sequence

Methylated DNA

GUIDE-seqOligo insert

DNAGenome-wide, unbiased identi�cation of DSBs enabled by sequencing (GUIDE-seq)

Genome DNA dsOligo tag integrat-ed in live cells

DNA isolationRandom shearing

End repairAdaptor ligation

dsOligo-speci�c ampli�cation

dsOligo insert

Oligo tagUMI

P5 Index 2

Index 1

Preparation of acylated RNA for biotin–streptavidin puri�cation. DIBO, dibenzocyclooxtyne

Biotin

Acylation

DIBO-biotin “click”

MINCE-seqSonication and MNase digestion

Streptavidin capture

DNAMapping in vivo nascent chromatin with EdU and sequencing (MINCE-seq)

Crosslink with formaldehyde Click reactionto attach biotin

Label with ethynyl deoxyuridine (EdU)

DNA extraction

Chase with Thymidine

Polymerase

Newly-formed chromatin Streptavidin

SSB-SeqSingle-strand break

DNAMap DNA single-strand breaks (SSB-Seq)

Genome DNA DNA isolation and random shearing Immunoprecipitate with anti-digoxigenin antibody

DNA Pol I, dU-digoxigenin, and dNTPs

DSB-SeqDouble-strand break

DNAMap DNA double-strand breaks (DSB-Seq)

Genome DNA DNA isolation and random shearing Capture on streptavidin beadsTdT and biotinylated-dUTP

scAba-seqDNADetect 5hmC marks in single cells

with AbaSI nuclease (scAba-seq)Glucosylated 5-hmC

5hmc residues

AbaSI Ligate Pool T7 ampli�cationPrimer

Illumina 5’ adaptorT7 promoter

Adaptor with cell-speci�c barcodeSingle cell

Droplet-based single-cell ChIP-seq (Drop-ChIP)

Drop-ChIPscChIP-seq

Single cell

Barcoded sequences from single cells

Cell suspension

Droplet with unique oligos

Load single cells into droplets with lysis bu�er and MNase

Fuse droplets Pool all droplets SequenceChromatin immuno-precipitation

Single cell

scATAC-Seq(Microfluidics)

Fragmented and primed DNASingle-cell assay for transposase accessible chromatin (scATAC-Seq)

Lyse and introduce Tn5 transposase

Pool libraries from all cells

Amplify with cell-speci�c barcodes

Insert in regions of open chromatinCell suspension

Micro�uidics device

Isolate single cell

Very rare mutationSafe-SeqS

DNA Shear

Mutation

Amplify and solid phase capture

SequenceSafe-sequencing system is a unique molecular identi�er (UMI) approach to detect rare variants (Safe-SeqS)

Adaptor ligation Randomly sheared ends serve as UMIs

Align sequences and determine actual ratio

True mutant

FiT-seqHeat 40°C in SDS DNAPuri�cationFixed-tissue chromatin immuno-

precipitation sequencing (FiT-Seq)Depara�nation and rehydration

FFPE-�xed chromatin

Proteinase K digestion

Enzyme inactivation

Sonicate Soluble extract

Immunoprecipitate Cromatin elution

PAT-ChIPMNase digestion DNAPuri�cationPathology tissue chromatin

immunoprecipitation (PAT-ChIP)Depara�nation and rehydration

FFPE-�xed chromatin

Sonicate Soluble extract

Immunoprecipitate and chromatin elution

Reverse crosslink and proteinase K digestion

UMI-4C

Ligation Sonicate Single end adaptor ligation

Reverse crosslink and proteinase K digestion

HC DpnII digestion

Nested PCR ampli�cation DNATargeted chromosome conformation capture (4C) with unique molecular identi�ers (UMI-4C)

Crosslink proteins and DNA

Adaptor Universal primerDS

primerUS primer

BLESSDouble-strand break

DNABreaks labeling and enrichment on streptavidin and sequencing (BLESS)

Genome DNA DNA isolation and random shearing

Capture on streptavidin beads

Biotinylated proximal primer

Distal primer

Digest with I-SceI and PCR

Ligate primer

TTTTTTTT

Dige-nome-seq

Genome Cas9 target

In vitro Cas9-digested whole-ge-nome sequencing (Digenome-seq)

Sequence Align and determine sequence breaks

Target site digestion

Wild typeDeletion

Insert scRC-SeqGenomic DNA Enriched library

Novel retrotrans-position events

Retrotransposon binding site

Single cell retrotransposon capture sequencing (scRC-Seq)

Cell suspension

FACS isolation

Pick nuclei

Whole genome ampli�cation

Create sequencing library

Sequence captureNucleus

EpiRADseqGenome Restriction sites

Double digest restriction-site associated DNA marker generation (ddRADseq) with a methyla-tion-sensitive restriction enzyme (EpiRADseq)

Second restriction digest with methylation-sensitive HpaII

Add barcoded adapters Add P2 adapter

Amplify DNA

ddRADseqGenome Restriction sites

Double digest restriction-site associated DNA marker generation (ddRADseq)

Second restriction digest Add barcoded adapters Add P2 adapter

Amplify DNA

hyRADGenome DNA to be capturedHigh quality DNA

Hybridization RAD (hyRAD) for degraded DNA

Shotgun library Hybridize to probesPrepare RAD-seq library and size select

DNAAdaptor removal and labeling

Biotinylated probes

GenomeMDAIMS-MDAMIDAS

Hybridize primers

Nascent replication fork

Phi 29 Phi 29 S1 nuclease Ampli�ed DNA

3’ blocked random hexamer primers

Synthesis SynthesisMultiple displacement ampli�cation (MDA). Immunomagnetic separation for targeted bacterial enrichment for MDA (IMS-MDA) Microwell displacement ampli�cation system (MIDAS)

T7 promoterRead primer

THS-seqEnd �ll-in and IVT ampli�cation

Add barcodes and sequencing adaptorsTransposome hypersensitive site

sequencing (THS-seq)Tn5 TransposomeOpen DNA dsDNA synthesisInsert in regions of open chromatin Purify

Single cellscATAC-Seq(Cell index)

DNASingle-cell assay for transposase accessible chromatin (scATAC-Seq)

Barcode each well with Tn5 transposase

Cell suspension Isolate Nuclei Split sample

Pool and dilute

Split sample PCR-barcode every well

Pool for library prep

SMDBSingle-molecule droplet barcoding (SMDB)

DNA templates Single template encapsulation

Template ampli�cation Template fragmentation Barcode every droplet Pool for library prep

Digoxigenin

O OSNS

RNAprimer

NSCRNascent strand capture and release (NSCR)

DNA replication bubble Denaturation and size-selection

5’-biotinylation Streptavidin pull-down RNase I digestion

Isolate and amplify SNS

Biotin

5fC-AI-SH

5fC-AI

N3 5fC

AI-mediated cyclization labeling in fC-CET

BisChIP-SeqChIP-BS-seq

ImmunoprecipitateSonicate DNABisul�te conversion

C GTCT

C GTUT

Bisul�te

C GTTT

Bisul�te-treated chromatin immuno-precipitated DNA (BisChIP-seq) and ChIP-BS-seq), to correlate protein modi�cations with DNA methylation

DNA-protein complex with methylated histones and methylated DNA

Purify DNA and shear

Repli SeqNascent DNA

Run-on with analog Sort cells and lyse DNARepli Seq—to map temporally ordered replicating DNA

PurifyBead coated with anti-BrdU antibody

EluteEnd Repair

NS-seqNascent DNA

DNA replication origin Lambda 5´ to 3´ exodeoxyribonuclease (λ-exo) DNANascent strand sequencing (NS-seq) to discover DNA replication origins and G4 structures

AmplifyPurifyDigestion

DNA...ddRADseq Peterson B. K. et al. (2012) PLoS One 7: e37135 Digenome-seq Kim D et al. (2015) Nat...

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