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Basic Principles of Bioinformatics for Next-Generation Sequencing Molecular Testing in Oncology

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Practical Medical Oncology Textbook

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Abstract

The advent of next-generation sequencing platform made possible a deeper knowledge of the genetic bases of cancer, which actually is considered a disease affecting genome.

Despite the lowering of costs it is possible to deep sequence hundreds of genes in a single experiment producing a very large amount of data.

Molecular testing has opened the possibility to design genome-driven clinical trials, e.g. enrolling patients in study for the pattern of genetic alterations.

Thus, bioinformatic skills are essential to produce reliable results. Basic knowledge of the essential bioinformatic steps in identification of a mutation and its biological role could be helpful in the management of molecular testing results. Then, typical bioinformatic pipelines, from raw data to clinical reporting of a mutations, will be described.

Given the importance of the analysis workflow, the urgency to draft guidelines for bioinformatic quality checks and their reproducibility is emerging. Many projects are available to manage this issue, but a consensus has not been reached yet.

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References

  1. Hyman DM, Taylor BS, Baselga J. Implementing genome-driven oncology. Cell. 2017;168(4):584–99. https://doi.org/10.1016/j.cell.2016.12.015. Review. PubMed PMID: 28187282; PubMed Central PMCID: PMC5463457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Russo A, Incorvaia L, Malapelle U, et al. The tumor-agnostic treatment for patients with solid tumors: a position paper on behalf of the AIOM-SIAPEC/IAP-SIBIOC-SIF italian scientific societies [published online ahead of print, 2021 Aug 6]. Crit Rev Oncol Hematol. 2021;103436. https://doi.org/10.1016/j.critrevonc.2021.103436.

  3. Marziali A, Akeson M. New DNA sequencing methods. Annu Rev Biomed Eng. 2001;3:195–223. Review. PubMed PMID: 11447062.

    Article  CAS  PubMed  Google Scholar 

  4. Service RF. Gene sequencing. The race for the $1000 genome. Science. 2006;311(5767):1544–6. PubMed PMID: 16543431.

    Article  PubMed  Google Scholar 

  5. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. [PMID: 19451168].

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25. https://doi.org/10.1186/gb-2009-10-3-r25. Epub 2009 Mar 4. PubMed PMID:19261174; PubMed Central PMCID: PMC2690996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guo Y, Li J, Li CI, Long J, Samuels DC, Shyr Y. The effect of strand bias in illumina short-read sequencing data. BMC Genomics. 2012;13:666. https://doi.org/10.1186/1471-2164-13-666. PubMed PMID: 23176052; PubMed Central PMCID:PMC3532123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. D’Aurizio R, Pippucci T, Tattini L, Giusti B, Pellegrini M, Magi A. Enhancedcopy number variants detection from whole-exome sequencing data using EXCAVATOR2. Nucleic Acids Res. 2016;44(20):e154. Epub 2016 Aug 9. PubMed PMID:27507884; PubMed Central PMCID: PMC5175347.

    PubMed  PubMed Central  Google Scholar 

  9. 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. Break dancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods. 2009;6(9):677–81. https://doi.org/10.1038/nmeth.1363. Epub 2009 Aug 9. PubMed PMID: 19668202; PubMed Central PMCID: PMC3661775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ye K, Schulz MH, Long Q, Apweiler R, Ning Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009;25(21):2865–71. https://doi.org/10.1093/bioinformatics/btp394. Epub 2009 June 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Russo A, Incorvaia L, Del Re M, et al. The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian Scientific Societies [published online ahead of print, 2021 Jun 3]. ESMO Open. 2021;6(3):100164. https://doi.org/10.1016/j.esmoop.2021.100164.

  12. Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy forcancer. Clin Chem. 2015;61(1):112–23. https://doi.org/10.1373/clinchem.2014.222679. Epub 2014 Nov 11. Review. PubMed PMID: 25388429.

    Article  CAS  PubMed  Google Scholar 

  13. Chen S, Huang T, Zhou Y, Han Y, Xu M, Gu J. AfterQC: automatic filtering,trimming, error removing and quality control for fastq data. BMC Bioinformatics. 2017;18(Suppl 3):80. https://doi.org/10.1186/s12859-017-1469-3. PubMed PMID:28361673; PubMed Central PMCID: PMC5374548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Meldrum C, Doyle MA, Tothill RW. Next-generation sequencing for cancerdiagnostics: a practical perspective. Clin Biochem Rev. 2011;32(4):177–95. PubMed PMID: 22147957; PubMed Central PMCID: PMC3219767.

    PubMed  PubMed Central  Google Scholar 

  15. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. Anultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20(5):548–54. https://doi.org/10.1038/nm.3519. Epub 2014 Apr 6. PubMed PMID: 24705333; PubMed Central PMCID: PMC4016134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hardwick SA, Deveson IW, Mercer TR. Reference standards for next-generation sequencing. Nat Rev Genet. 2017;18(8):473–84. https://doi.org/10.1038/nrg.2017.44. Epub 2017 June 19. Review. PubMed PMID: 28626224. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, HegdeM, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. https://doi.org/10.1038/gim.2015.30. Epub 2015 Mar 5. PubMed PMID: 25741868; PubMed Central PMCID: PMC4544753.

  17. Amendola LM, Jarvik GP, Leo MC, McLaughlin HM, Akkari Y, Amaral MD, Berg JS, Biswas S, Bowling KM, Conlin LK, Cooper GM, Dorschner MO, Dulik MC, Ghazani AA, Ghosh R, Green RC, Hart R, Horton C, Johnston JJ, Lebo MS, Milosavljevic A, Ou J, Pak CM, Patel RY, Punj S, Richards CS, Salama J, Strande NT, Yang Y, Plon SE, Biesecker LG, Rehm HL. Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium. Am J Hum Genet. 2016;98(6):1067–76. https://doi.org/10.1016/j.ajhg.2016.03.024. Epub 2016 May 12. Erratum in: Am J Hum Genet. 2016;99(1):247. PubMed PMID: 27181684; PubMed Central PMCID: PMC4908185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sandve GK, Nekrutenko A, Taylor J, Hovig E. Ten simple rules for reproducible computational research. PLoS Comput Biol. 2013;9(10):e1003285. https://doi.org/10.1371/journal.pcbi.1003285. Epub 2013 Oct 24.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Molecular Diagnostics and Pharmacogenetics Unit – IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy

    Simona De Summa & Stefania Tommasi

Authors
  1. Simona De Summa
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  2. Stefania Tommasi
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Correspondence to Stefania Tommasi .

Editor information

Editors and Affiliations

  1. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. Oncology Department, University of Antwerp, Edegem, Belgium

    Marc Peeters

  3. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  4. Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai System & Icahn School of Medicine, Mount Sinai, NY, USA

    Christian Rolfo

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De Summa, S., Tommasi, S. (2021). Basic Principles of Bioinformatics for Next-Generation Sequencing Molecular Testing in Oncology. In: Russo, A., Peeters, M., Incorvaia, L., Rolfo, C. (eds) Practical Medical Oncology Textbook. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-030-56051-5_17

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  • DOI: https://doi.org/10.1007/978-3-030-56051-5_17

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-56050-8

  • Online ISBN: 978-3-030-56051-5

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