Skip to main content
SpringerLink
Log in

Next-Generation Sequencing (NGS) in Anatomic Pathology Discovery and Practice

  • Protocol
  • First Online:
Molecular Histopathology and Tissue Biomarkers in Drug and Diagnostic Development

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

  • 1064 Accesses

Abstract

Next-generation sequencing (NGS), also known as massively parallel sequencing (MPS), is a family of emerging and powerful technologies that generate an enormous amount of nucleic acid sequence data on a time scale and at a cost that is becoming compatible with routine clinical diagnostic applications. NGS relies upon selective amplification or capture of a complex population of nucleic acid molecules within a biological sample. Simultaneous sequencing reactions generate a variably broad and deep digital readout of sequences in the sample, representing specific regions of genes such as exons, a class of RNAs, or whole genomes. NGS can be viewed as a special type of multianalyte “omics” test that overturns the “one-question/one-test” paradigm prevalent in pathology and laboratory medicine for over a century. It has the potential to address thousands of clinically relevant questions at once while also serving as a transformative, hypothesis-generating discovery tool. The power of NGS to generate massive datasets, which by their sheer size and complexity can approach the level of biological complexity within the tissue sample itself, qualifies it as a “disruptive technology” that will task the medical establishment, particularly pathology and laboratory medicine professionals who generate and interpret the data, to implement it in clinical settings. There remain numerous challenges to the routine implementation of NGS technologies in drug development and clinical diagnostics, including scientific/technical, medical, financial, legal/regulatory, and ethical hurdles.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Dunstan RW, Wharton KA Jr, Quigley C, Lowe A (2011) The use of immunohistochemistry for biomarker assessment – can it compete with other technologies? Toxicol Pathol 39(6):988–1002. doi:10.1177/0192623311419163

    Article  PubMed  Google Scholar 

  2. Vaandrager JW, Schuuring E, Zwikstra E, de Boer CJ, Kleiverda KK, van Krieken JH, Kluin-Nelemans HC, van Ommen GJ, Raap AK, Kluin PM (1996) Direct visualization of dispersed 11q13 chromosomal translocations in mantle cell lymphoma by multicolor DNA fiber fluorescence in situ hybridization. Blood 88(4):1177–1182

    CAS  PubMed  Google Scholar 

  3. Wang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A, Wu X, Vo HT, Ma XJ, Luo Y (2012) RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn 14(1):22–29. doi:10.1016/j.jmoldx.2011.08.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Hanna JA, Wimberly H, Kumar S, Slack F, Agarwal S, Rimm DL (2012) Quantitative analysis of microRNAs in tissue microarrays by in situ hybridization. Biotechniques 52(4):235–245. doi:10.2144/000113837

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Gridelli C, de Marinis F, Cappuzzo F, Di Maio M, Hirsch FR, Mok T, Morgillo F, Rosell R, Spigel DR, Yang JC, Ciardiello F (2014) Treatment of advanced non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation or ALK gene rearrangement: results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Canc 15(3):173–181. doi:10.1016/j.cllc.2013.12.002

    Article  CAS  Google Scholar 

  6. Gridelli C, Peters S, Sgambato A, Casaluce F, Adjei AA, Ciardiello F (2014) ALK inhibitors in the treatment of advanced NSCLC. Canc Treat Rev 40(2):300–306. doi:10.1016/j.ctrv.2013.07.002

    Article  CAS  Google Scholar 

  7. Parsons BL, Myers MB (2013) Personalized cancer treatment and the myth of KRAS wild-type colon tumors. Discov Med 15(83):259–267

    PubMed  Google Scholar 

  8. Kiechle FL, Zhang X, Holland-Staley CA (2004) The -omics era and its impact. Arch Pathol Lab Med 128(12):1337–1345. doi:10.1043/1543-2165(2004)128<1337:TOEAII>2.0.CO;2

    PubMed  Google Scholar 

  9. Zhang Z (2012) An in vitro diagnostic multivariate index assay (IVDMIA) for ovarian cancer: harvesting the power of multiple biomarkers. Rev Obstet Gynecol 5(1):35–41

    PubMed Central  PubMed  Google Scholar 

  10. Micheel CM, Nass SJ, Omenn GS, Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials, Board on Health Care Services, Board on Health Sciences Policy, Institute of Medicine (eds) (2012) Evolution of translational omics: lessons learned and the path forward. National Academies Press, Washington, DC, PMID: 24872966

    Google Scholar 

  11. McShane LM, Cavenagh MM, Lively TG, Eberhard DA, Bigbee WL, Williams PM, Mesirov JP, Polley MY, Kim KY, Tricoli JV, Taylor JM, Shuman DJ, Simon RM, Doroshow JH, Conley BA (2013) Criteria for the use of omics-based predictors in clinical trials. Nature 502(7471):317–320. doi:10.1038/nature12564

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Prat A, Perou CM (2011) Deconstructing the molecular portraits of breast cancer. Mol Oncol 5(1):5–23. doi:10.1016/j.molonc.2010.11.003

    Article  CAS  PubMed  Google Scholar 

  13. Roschewski M, Staudt LM, Wilson WH (2014) Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol 11(1):12–23. doi:10.1038/nrclinonc.2013.197

    Article  CAS  PubMed  Google Scholar 

  14. van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Batlle E, Coudreuse D, Haramis AP, Tjon-Pon-Fong M, Moerer P, van den Born M, Soete G, Pals S, Eilers M, Medema R, Clevers H (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111(2):241–250

    Article  PubMed  Google Scholar 

  15. Guarnaccia M, Gentile G, Alessi E, Schneider C, Petralia S, Cavallaro S (2014) Is this the real time for genomics? Genomics 103(2–3):177–182. doi:10.1016/j.ygeno.2014.02.003

    Article  CAS  PubMed  Google Scholar 

  16. Carlson JJ, Roth JA (2013) The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res Treat 141(1):13–22. doi:10.1007/s10549-013-2666-z

    Article  PubMed Central  PubMed  Google Scholar 

  17. Sahebjam S, Aloyz R, Pilavdzic D, Brisson ML, Ferrario C, Bouganim N, Cohen V, Miller WH Jr, Panasci LC (2011) Ki 67 is a major, but not the sole determinant of Oncotype Dx recurrence score. Br J Cancer 105(9):1342–1345. doi:10.1038/bjc.2011.402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Malone JH, Oliver B (2011) Microarrays, deep sequencing and the true measure of the transcriptome. BMC Biol 9:34. doi:10.1186/1741-7007-9-34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kilpivaara O, Aaltonen LA (2013) Diagnostic cancer genome sequencing and the contribution of germline variants. Science 339(6127):1559–1562. doi:10.1126/science.1233899

    Article  CAS  PubMed  Google Scholar 

  20. Maes E, Broeckx V, Mertens I, Sagaert X, Prenen H, Landuyt B, Schoofs L (2013) Analysis of the formalin-fixed paraffin-embedded tissue proteome: pitfalls, challenges, and future prospectives. Amino Acids 45(2):205–218. doi:10.1007/s00726-013-1494-0

    Article  CAS  PubMed  Google Scholar 

  21. Peiro-Chova L, Pena-Chilet M, Lopez-Guerrero JA, Garcia-Gimenez JL, Alonso-Yuste E, Burgues O, Lluch A, Ferrer-Lozano J, Ribas G (2013) High stability of microRNAs in tissue samples of compromised quality. Virchows Arch 463(6):765–774. doi:10.1007/s00428-013-1485-2

    Article  CAS  PubMed  Google Scholar 

  22. Nam SK, Im J, Kwak Y, Han N, Nam KH, Seo AN, Lee HS (2014) Effects of fixation and storage of human tissue samples on nucleic Acid preservation. Korean J Pathol 48(1):36–42. doi:10.4132/KoreanJPathol.2014.48.1.36

    Article  PubMed Central  PubMed  Google Scholar 

  23. Spencer DH, Sehn JK, Abel HJ, Watson MA, Pfeifer JD, Duncavage EJ (2013) Comparison of clinical targeted next-generation sequence data from formalin-fixed and fresh-frozen tissue specimens. J Mol Diagn 15(5):623–633. doi:10.1016/j.jmoldx.2013.05.004

    Article  CAS  PubMed  Google Scholar 

  24. Hewitt SM, Lewis FA, Cao Y, Conrad RC, Cronin M, Danenberg KD, Goralski TJ, Langmore JP, Raja RG, Williams PM, Palma JF, Warrington JA (2008) Tissue handling and specimen preparation in surgical pathology: issues concerning the recovery of nucleic acids from formalin-fixed, paraffin-embedded tissue. Arch Pathol Lab Med 132(12):1929–1935. doi:10.1043/1543-2165-132.12.1929

    PubMed  Google Scholar 

  25. Giusti L, Lucacchini A (2013) Proteomic studies of formalin-fixed paraffin-embedded tissues. Expert Rev Proteomics 10(2):165–177. doi:10.1586/epr.13.3

    Article  CAS  PubMed  Google Scholar 

  26. Nielsen T, Wallden B, Schaper C, Ferree S, Liu S, Gao D, Barry G, Dowidar N, Maysuria M, Storhoff J (2014) Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer 14:177. doi:10.1186/1471-2407-14-177

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kap M, Smedts F, Oosterhuis W, Winther R, Christensen N, Reischauer B, Viertler C, Groelz D, Becker KF, Zatloukal K, Langer R, Slotta-Huspenina J, Bodo K, de Jong B, Oelmuller U, Riegman P (2011) Histological assessment of PAXgene tissue fixation and stabilization reagents. PLoS One 6(11):e27704. doi:10.1371/journal.pone.0027704

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Belloni B, Lambertini C, Nuciforo P, Phillips J, Bruening E, Wong S, Dummer R (2013) Will PAXgene substitute formalin? A morphological and molecular comparative study using a new fixative system. J Clin Pathol 66(2):124–135. doi:10.1136/jclinpath-2012-200983

    Article  CAS  PubMed  Google Scholar 

  29. Biesecker LG (2010) Exome sequencing makes medical genomics a reality. Nat Genet 42(1):13–14. doi:10.1038/ng0110-13

    Article  CAS  PubMed  Google Scholar 

  30. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J (2011) Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12(11):745–755. doi:10.1038/nrg3031

    Article  CAS  PubMed  Google Scholar 

  31. Cassidy LD, Venkitaraman AR (2012) Genome instability mechanisms and the structure of cancer genomes. Curr Opin Genet Dev 22(1):10–13. doi:10.1016/j.gde.2012.02.003

    Article  CAS  PubMed  Google Scholar 

  32. Chiu CY (2013) Viral pathogen discovery. Curr Opin Microbiol 16(4):468–478. doi:10.1016/j.mib.2013.05.001

    Article  CAS  PubMed  Google Scholar 

  33. Fortes GG, Speller CF, Hofreiter M, King TE (2013) Phenotypes from ancient DNA: approaches, insights and prospects. Bioessays 35(8):690–695. doi:10.1002/bies.201300036

    Article  CAS  PubMed  Google Scholar 

  34. Zaura E (2012) Next-generation sequencing approaches to understanding the oral microbiome. Adv Dent Res 24(2):81–85. doi:10.1177/0022034512449466

    Article  CAS  PubMed  Google Scholar 

  35. Madar S, Goldstein I, Rotter V (2013) “Cancer associated fibroblasts” – more than meets the eye. Trends Mol Med 19(8):447–453. doi:10.1016/j.molmed.2013.05.004

    Article  CAS  PubMed  Google Scholar 

  36. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, Girsberger S, Lehmann T, Passweg J, Stern M, Beisel C, Kralovics R, Skoda RC (2014) Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 123(14):2220–2228. doi:10.1182/blood-2013-11-537167

    Article  CAS  PubMed  Google Scholar 

  37. Villamor N, Lopez-Guillermo A, Lopez-Otin C, Campo E (2013) Next-generation sequencing in chronic lymphocytic leukemia. Semin Hematol 50(4):286–295. doi:10.1053/j.seminhematol.2013.09.005

    Article  CAS  PubMed  Google Scholar 

  38. Schrijver I, Aziz N, Farkas DH, Furtado M, Gonzalez AF, Greiner TC, Grody WW, Hambuch T, Kalman L, Kant JA, Klein RD, Leonard DG, Lubin IM, Mao R, Nagan N, Pratt VM, Sobel ME, Voelkerding KV, Gibson JS (2012) Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology. J Mol Diagn 14(6):525–540. doi:10.1016/j.jmoldx.2012.04.006

    Article  CAS  PubMed  Google Scholar 

  39. Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA, Chaib H, Merker JD, Goldfeder RL, Enns GM, David SP, Pakdaman N, Ormond KE, Caleshu C, Kingham K, Klein TE, Whirl-Carrillo M, Sakamoto K, Wheeler MT, Butte AJ, Ford JM, Boxer L, Ioannidis JP, Yeung AC, Altman RB, Assimes TL, Snyder M, Ashley EA, Quertermous T (2014) Clinical interpretation and implications of whole-genome sequencing. JAMA 311(10):1035–1045. doi:10.1001/jama.2014.1717

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, International Human Genome Sequencing C (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921. doi: 10.1038/35057062

  41. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 291(5507):1304–1351. doi: 10.1126/science.1058040

  42. Meyerson M, Gabriel S, Getz G (2010) Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 11(10):685–696. doi:10.1038/nrg2841

    Article  CAS  PubMed  Google Scholar 

  43. Yates LR, Campbell PJ (2012) Evolution of the cancer genome. Nat Rev Genet 13(11):795–806. doi:10.1038/nrg3317

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM (2013) Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 369(16):1502–1511. doi:10.1056/NEJMoa1306555

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. MacConaill LE (2013) Existing and emerging technologies for tumor genomic profiling. J Clin Oncol 31(15):1815–1824. doi:10.1200/JCO.2012.46.5948

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Chin EL, da Silva C, Hegde M (2013) Assessment of clinical analytical sensitivity and specificity of next-generation sequencing for detection of simple and complex mutations. BMC Genet 14:6. doi:10.1186/1471-2156-14-6

    Article  PubMed Central  PubMed  Google Scholar 

  47. Tsiatis AC, Norris-Kirby A, Rich RG, Hafez MJ, Gocke CD, Eshleman JR, Murphy KM (2010) Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations: diagnostic and clinical implications. J Mol Diagn 12(4):425–432. doi:10.2353/jmoldx.2010.090188

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Krueger F, Kreck B, Franke A, Andrews SR (2012) DNA methylome analysis using short bisulfite sequencing data. Nat Methods 9(2):145–151. doi:10.1038/nmeth.1828

    Article  CAS  PubMed  Google Scholar 

  49. Koboldt DC, Larson DE, Chen K, Ding L, Wilson RK (2012) Massively parallel sequencing approaches for characterization of structural variation. Methods Mol Biol 838:369–384. doi:10.1007/978-1-61779-507-7_18

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11(1):31–46. doi:10.1038/nrg2626

    Article  CAS  PubMed  Google Scholar 

  51. Ozsolak F (2012) Third-generation sequencing techniques and applications to drug discovery. Expert Opin Drug Discov 7(3):231–243. doi:10.1517/17460441.2012.660145

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Gut IG (2013) New sequencing technologies. Clin Transl Oncol 15(11):879–881. doi:10.1007/s12094-013-1073-6

    Article  CAS  PubMed  Google Scholar 

  53. Xu MY, Aragon AD, Mascarenas MR, Torrez-Martinez N, Edwards JS (2010) Dual primer emulsion PCR for next- generation DNA sequencing. Biotechniques 48(5):409–412. doi:10.2144/000113423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DM, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Chiara ECM, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ, Goddard CP, Golda GS, Granieri PA, Green DE, Gustafson DL, Hansen NF, Harnish K, Haudenschild CD, Heyer NI, Hims MM, Ho JT, Horgan AM, Hoschler K, Hurwitz S, Ivanov DV, Johnson MQ, James T, Huw Jones TA, Kang GD, Kerelska TH, Kersey AD, Khrebtukova I, Kindwall AP, Kingsbury Z, Kokko-Gonzales PI, Kumar A, Laurent MA, Lawley CT, Lee SE, Lee X, Liao AK, Loch JA, Lok M, Luo S, Mammen RM, Martin JW, McCauley PG, McNitt P, Mehta P, Moon KW, Mullens JW, Newington T, Ning Z, Ling Ng B, Novo SM, O’Neill MJ, Osborne MA, Osnowski A, Ostadan O, Paraschos LL, Pickering L, Pike AC, Pike AC, Chris Pinkard D, Pliskin DP, Podhasky J, Quijano VJ, Raczy C, Rae VH, Rawlings SR, Chiva Rodriguez A, Roe PM, Rogers J, Rogert Bacigalupo MC, Romanov N, Romieu A, Roth RK, Rourke NJ, Ruediger ST, Rusman E, Sanches-Kuiper RM, Schenker MR, Seoane JM, Shaw RJ, Shiver MK, Short SW, Sizto NL, Sluis JP, Smith MA, Ernest Sohna Sohna J, Spence EJ, Stevens K, Sutton N, Szajkowski L, Tregidgo CL, Turcatti G, Vandevondele S, Verhovsky Y, Virk SM, Wakelin S, Walcott GC, Wang J, Worsley GJ, Yan J, Yau L, Zuerlein M, Rogers J, Mullikin JC, Hurles ME, McCooke NJ, West JS, Oaks FL, Lundberg PL, Klenerman D, Durbin R, Smith AJ (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456(7218):53–59. doi: 10.1038/nature07517

  55. Aird D, Ross MG, Chen WS, Danielsson M, Fennell T, Russ C, Jaffe DB, Nusbaum C, Gnirke A (2011) Analyzing and minimizing PCR amplification bias in Illumina sequencing libraries. Genome Biol 12(2):R18. doi:10.1186/gb-2011-12-2-r18

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Oyola SO, Otto TD, Gu Y, Maslen G, Manske M, Campino S, Turner DJ, Macinnis B, Kwiatkowski DP, Swerdlow HP, Quail MA (2012) Optimizing Illumina next-generation sequencing library preparation for extremely AT-biased genomes. BMC Genomics 13:1. doi:10.1186/1471-2164-13-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Mamanova L, Coffey AJ, Scott CE, Kozarewa I, Turner EH, Kumar A, Howard E, Shendure J, Turner DJ (2010) Target-enrichment strategies for next-generation sequencing. Nat Methods 7(2):111–118. doi:10.1038/nmeth.1419

    Article  CAS  PubMed  Google Scholar 

  58. Lasho T, Johnson SH, Smith DI, Crispino JD, Pardanani A, Vasmatzis G, Tefferi A (2013) Identification of submicroscopic genetic changes and precise breakpoint mapping in myelofibrosis using high resolution mate-pair sequencing. Am J Hematol 88(9):741–746. doi:10.1002/ajh.23495

    Article  CAS  PubMed  Google Scholar 

  59. Levy-Sakin M, Ebenstein Y (2013) Beyond sequencing: optical mapping of DNA in the age of nanotechnology and nanoscopy. Curr Opin Biotechnol 24(4):690–698. doi:10.1016/j.copbio.2013.01.009

    Article  CAS  PubMed  Google Scholar 

  60. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, Leamon JH, Johnson K, Milgrew MJ, Edwards M, Hoon J, Simons JF, Marran D, Myers JW, Davidson JF, Branting A, Nobile JR, Puc BP, Light D, Clark TA, Huber M, Branciforte JT, Stoner IB, Cawley SE, Lyons M, Fu Y, Homer N, Sedova M, Miao X, Reed B, Sabina J, Feierstein E, Schorn M, Alanjary M, Dimalanta E, Dressman D, Kasinskas R, Sokolsky T, Fidanza JA, Namsaraev E, McKernan KJ, Williams A, Roth GT, Bustillo J (2011) An integrated semiconductor device enabling non-optical genome sequencing. Nature 475(7356):348–352. doi:10.1038/nature10242

    Article  CAS  PubMed  Google Scholar 

  61. Keightley PD (2012) Rates and fitness consequences of new mutations in humans. Genetics 190(2):295–304. doi:10.1534/genetics.111.134668

    Article  PubMed Central  PubMed  Google Scholar 

  62. Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, Pallen MJ (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 30(5):434–439. doi:10.1038/nbt.2198

    Article  CAS  PubMed  Google Scholar 

  63. Meacham F, Boffelli D, Dhahbi J, Martin DI, Singer M, Pachter L (2011) Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12:451. doi:10.1186/1471-2105-12-451

    Article  PubMed Central  PubMed  Google Scholar 

  64. Grossmann V, Roller A, Klein HU, Weissmann S, Kern W, Haferlach C, Dugas M, Haferlach T, Schnittger S, Kohlmann A (2013) Robustness of amplicon deep sequencing underlines its utility in clinical applications. J Mol Diagn 15(4):473–484. doi:10.1016/j.jmoldx.2013.03.003

    Article  CAS  PubMed  Google Scholar 

  65. Ellard S, Patrinos GP, Oetting WS (2013) Clinical applications of next-generation sequencing: the 2013 human genome variation society scientific meeting. Hum Mutat 34(11):1583–1587. doi:10.1002/humu.22400

    Article  PubMed  Google Scholar 

  66. Torri F, Dinov ID, Zamanyan A, Hobel S, Genco A, Petrosyan P, Clark AP, Liu Z, Eggert P, Pierce J, Knowles JA, Ames J, Kesselman C, Toga AW, Potkin SG, Vawter MP, Macciardi F (2012) Next generation sequence analysis and computational genomics using graphical pipeline workflows. Genes 3(3):545–575. doi:10.3390/genes3030545

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Lin Y, Li J, Shen H, Zhang L, Papasian CJ, Deng HW (2011) Comparative studies of de novo assembly tools for next-generation sequencing technologies. Bioinformatics 27(15):2031–2037. doi:10.1093/bioinformatics/btr319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Li H, Homer N (2010) A survey of sequence alignment algorithms for next-generation sequencing. Brief Bioinform 11(5):473–483. doi:10.1093/bib/bbq015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Van Allen EM, Wagle N, Levy MA (2013) Clinical analysis and interpretation of cancer genome data. J Clin Oncol 31(15):1825–1833. doi:10.1200/JCO.2013.48.7215

    Article  PubMed  Google Scholar 

  70. Ruffalo M, LaFramboise T, Koyuturk M (2011) Comparative analysis of algorithms for next-generation sequencing read alignment. Bioinformatics 27(20):2790–2796. doi:10.1093/bioinformatics/btr477

    Article  CAS  PubMed  Google Scholar 

  71. Chin L, Hahn WC, Getz G, Meyerson M (2011) Making sense of cancer genomic data. Genes Dev 25(6):534–555. doi:10.1101/gad.2017311

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Gullapalli RR, Desai KV, Santana-Santos L, Kant JA, Becich MJ (2012) Next generation sequencing in clinical medicine: Challenges and lessons for pathology and biomedical informatics. J Pathol Informat 3:40. doi:10.4103/2153-3539.103013

    Article  Google Scholar 

  73. Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE, Molecular Subcommittee of the ALQAC (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 10(4):294–300. doi:10.1097/GIM.0b013e31816b5cae

    Article  CAS  PubMed  Google Scholar 

  74. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, Friez MJ, Funke BH, Hegde MR, Lyon E, Working Group of the American College of Medical G, Genomics Laboratory Quality Assurance C (2013) ACMG clinical laboratory standards for next-generation sequencing. Genet Med 15(9):733–747. doi:10.1038/gim.2013.92

    Article  PubMed Central  PubMed  Google Scholar 

  75. Tarczy-Hornoch P, Amendola L, Aronson SJ, Garraway L, Gray S, Grundmeier RW, Hindorff LA, Jarvik G, Karavite D, Lebo M, Plon SE, Van Allen E, Weck KE, White PS, Yang Y (2013) A survey of informatics approaches to whole-exome and whole-genome clinical reporting in the electronic health record. Genet Med 15(10):824–832. doi:10.1038/gim.2013.120

    Article  PubMed Central  PubMed  Google Scholar 

  76. Collins FS, Hamburg MA (2013) First FDA authorization for next-generation sequencer. N Engl J Med 369(25):2369–2371. doi:10.1056/NEJMp1314561

    Article  CAS  PubMed  Google Scholar 

  77. Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28(Suppl 1):S24–31. doi:10.1038/onc.2009.198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Stern HM (2012) Improving treatment of HER2-positive cancers: opportunities and challenges. Sci Transl Med 4(127):127rv2. doi:10.1126/scitranslmed.3001539

    Article  PubMed  Google Scholar 

  79. McShane LM, Cavenagh MM, Lively TG, Eberhard DA, Bigbee WL, Williams PM, Mesirov JP, Polley MY, Kim KY, Tricoli JV, Taylor JM, Shuman DJ, Simon RM, Doroshow JH, Conley BA (2013) Criteria for the use of omics-based predictors in clinical trials: explanation and elaboration. BMC Med 11:220. doi:10.1186/1741-7015-11-220

    Article  PubMed Central  PubMed  Google Scholar 

  80. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30–35. doi:10.1038/ng.499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O’Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG, American College of Medical Genetics and Genomics (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15(7):565–574. doi:10.1038/gim.2013.73

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O’Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (2011) A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 365(7):611–619. doi:10.1056/NEJMoa1104017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J (2013) Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 368(21):1971–1979. doi:10.1056/NEJMoa1213507

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Ledford H (2013) “Master protocol” aims to revamp cancer trials. Nature 498(7453):146–147. doi:10.1038/498146a

    Article  CAS  PubMed  Google Scholar 

  85. Cottrell CE, Al-Kateb H, Bredemeyer AJ, Duncavage EJ, Spencer DH, Abel HJ, Lockwood CM, Hagemann IS, O’Guin SM, Burcea LC, Sawyer CS, Oschwald DM, Stratman JL, Sher DA, Johnson MR, Brown JT, Cliften PF, George B, McIntosh LD, Shrivastava S, Nguyen TT, Payton JE, Watson MA, Crosby SD, Head RD, Mitra RD, Nagarajan R, Kulkarni S, Seibert K, Virgin HWT, Milbrandt J, Pfeifer JD (2014) Validation of a next-generation sequencing assay for clinical molecular oncology. J Mol Diagn 16(1):89–105. doi:10.1016/j.jmoldx.2013.10.002

    Article  CAS  PubMed  Google Scholar 

  86. Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Janne PA, Stephens PJ (2012) Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 18(3):382–384. doi:10.1038/nm.2673

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Grossmann V, Haferlach C, Weissmann S, Roller A, Schindela S, Poetzinger F, Stadler K, Bellos F, Kern W, Haferlach T, Schnittger S, Kohlmann A (2013) The molecular profile of adult T-cell acute lymphoblastic leukemia: mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL. Gene Chromosome Canc 52(4):410–422. doi:10.1002/gcc.22039

    Article  CAS  Google Scholar 

  88. Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497(7447):108–112. doi:10.1038/nature12065

    Article  CAS  PubMed  Google Scholar 

  89. Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D, Ebert BL (2011) Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 364(26):2496–2506. doi:10.1056/NEJMoa1013343

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Jeck WR, Parker J, Carson CC, Shields JM, Sambade MJ, Peters EC, Burd CE, Thomas NE, Chiang DY, Liu W, Eberhard DA, Ollila D, Grilley-Olson J, Moschos S, Neil Hayes D, Sharpless NE (2014) Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma. Pigment Cell Melanoma Res. doi:10.1111/pcmr.12238

    PubMed Central  PubMed  Google Scholar 

  91. Mutz KO, Heilkenbrinker A, Lonne M, Walter JG, Stahl F (2013) Transcriptome analysis using next-generation sequencing. Curr Opin Biotechnol 24(1):22–30. doi:10.1016/j.copbio.2012.09.004

    Article  CAS  PubMed  Google Scholar 

  92. Lee EJ, Luo J, Wilson JM, Shi H (2013) Analyzing the cancer methylome through targeted bisulfite sequencing. Cancer Lett 340(2):171–178. doi:10.1016/j.canlet.2012.10.040

    Article  CAS  PubMed  Google Scholar 

  93. Chen K, Wallis JW, McLellan MD, Larson DE, Kalicki JM, Pohl CS, McGrath SD, Wendl MC, Zhang Q, Locke DP, Shi X, Fulton RS, Ley TJ, Wilson RK, Ding L, Mardis ER (2009) BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods 6(9):677–681. doi:10.1038/nmeth.1363

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Ye K, Schulz MH, Long Q, Apweiler R, Ning Z (2009) Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25(21):2865–2871. doi:10.1093/bioinformatics/btp394

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Venkatraman ES, Olshen AB (2007) A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics 23(6):657–663. doi:10.1093/bioinformatics/btl646

    Article  CAS  PubMed  Google Scholar 

  96. Chiang DY, Getz G, Jaffe DB, O’Kelly MJ, Zhao X, Carter SL, Russ C, Nusbaum C, Meyerson M, Lander ES (2009) High-resolution mapping of copy-number alterations with massively parallel sequencing. Nat Methods 6(1):99–103. doi:10.1038/nmeth.1276

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4(7):1073–1081. doi:10.1038/nprot.2009.86

    Article  CAS  PubMed  Google Scholar 

  98. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249. doi:10.1038/nmeth0410-248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Liu X, Jian X, Boerwinkle E (2013) dbNSFP v2.0: a database of human non-synonymous SNVs and their functional predictions and annotations. Hum Mutat 34(9):E2393–2402. doi:10.1002/humu.22376

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA (2009) Circos: an information aesthetic for comparative genomics. Genome Res 19(9):1639–1645. doi:10.1101/gr.092759.109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Gargis AS, Kalman L, Berry MW, Bick DP, Dimmock DP, Hambuch T, Lu F, Lyon E, Voelkerding KV, Zehnbauer BA, Agarwala R, Bennett SF, Chen B, Chin EL, Compton JG, Das S, Farkas DH, Ferber MJ, Funke BH, Furtado MR, Ganova-Raeva LM, Geigenmuller U, Gunselman SJ, Hegde MR, Johnson PL, Kasarskis A, Kulkarni S, Lenk T, Liu CS, Manion M, Manolio TA, Mardis ER, Merker JD, Rajeevan MS, Reese MG, Rehm HL, Simen BB, Yeakley JM, Zook JM, Lubin IM (2012) Assuring the quality of next-generation sequencing in clinical laboratory practice. Nat Biotechnol 30(11):1033–1036. doi:10.1038/nbt.2403

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We’d like to acknowledge Edward Oakeley Ph.D. (Novartis AG) and Wendy Winckler Ph.D. (NIBRI) for critical reviews of the chapter, and Tiffany Liang for preparation of Fig. 1. UNCseq™ is funded in part by the UNC Lineberger Comprehensive Cancer Center’s University Cancer Research Fund. We would like to thank H. Shelton Earp III M.D., D. Neil Hayes M.D., M.P.H., Joel Parker Ph.D., Karen Weck M.D., and Nirali Patel M.D., for their leadership in the UNCseq™ program.

Author information

Authors and Affiliations

  1. Medical Laboratory, Genoptix, a Novartis Company, 2110 Rutherford Road, Carlsbad, CA, 92008, USA

    Matthew J. McGinniss

  2. Departments of Pathology and Laboratory Medicine, and of Pharmacology; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA

    David A. Eberhard

  3. Discovery and Investigative Pathology, Preclinical Safety, Novartis Institutes for BioMedical Research, Cambridge, MA, 02139, USA

    Keith A. Wharton Jr.

Authors
  1. Matthew J. McGinniss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David A. Eberhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keith A. Wharton Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith A. Wharton Jr. .

Editor information

Editors and Affiliations

  1. Flagship Biosciences, LLC, Westminster, Colorado, USA

    Steven J. Potts

  2. University of North Carolina, Chapel Hill, North Carolina, USA

    David A. Eberhard

  3. Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA

    Keith A. Wharton, Jr.

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

McGinniss, M.J., Eberhard, D.A., Wharton, K.A. (2014). Next-Generation Sequencing (NGS) in Anatomic Pathology Discovery and Practice. In: Potts, S., Eberhard, D., Wharton, Jr., K. (eds) Molecular Histopathology and Tissue Biomarkers in Drug and Diagnostic Development. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/7653_2014_39

Download citation

  • DOI: https://doi.org/10.1007/7653_2014_39

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2680-0

  • Online ISBN: 978-1-4939-2681-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation