SafeSeq NGS technology

Ultrasensitive sequencing for the detection of low abundant mutant DNA

SafeSeq NGS is a unique approach combining next generation sequencing technology with Sysmex Inostics´ expertise for highly sensitive mutation detection.

The right solution for the right question

Next-generation sequencing is a balancing act between sensitivity, genomic coverage, and cost. 

“Pan-cancer” and “universal” NGS tests sacrifice sensitivity and cost in favor of broad coverage and are not able to meet the needs of a wide range of applications.
 
Therefore, Sysmex Inostics has developed Plasma SafeSeq (PSS), a highly sensitive, customizable NGS solution for precision oncology:

  • PSS achieves high sensitivity and quantitative mutation calling by focusing on the most clinically relevant regions for different cancer types.
  • This also ensures minimal cost since excess data are not produced and wasted with every run as for large panels.
  • Custom panels allow true optimization of the diagnostic test to fit the clinical need.

Additional benefits

  • Proven Safe-SeqS technology combined with proprietary bioinformatic analysis to maximize analytic performance.
  • Compatible with both tissue specimens and plasma ctDNA -> decreased variability when analyzing matched specimens.
  • Built on Sysmex’s vast experience with plasma ctDNA analysis using our gold-standard OncoBEAM™ technology.

The importance of dynamic NGS tests

For NGS-based testings, real-world limitations mean there is little flexibility around sample input DNA amount and cost. As a result, a tradeoff exists between sensitivity and genomic coverage.

Coverage across a large area is possible at relatively low sensitivity; or, high sensitivity can be achieved for focused coverage of a few targets.  If both high sensitivity and comprehensive coverage are required, sample input and cost are increased.

Tumor monitoring

A novel application with unique needs

The emerging utility of tracking tumor-specific genetic alterations for tumor monitoring highlights the need for flexible tests.

Discovery of cancer-relevant mutations via tissue sequencing requires an assay that interrogates the most relevant set of targets for a particular type of cancer.  After somatic mutations have been characterized in the tissue, tracking via ctDNA analysis of serial blood draws requires extremely high sensitivity, and high resolution detection of the selected markers.

An NGS test used for disease monitoring must be able to modulate the balance between sensitivity and genomic coverage to ensure robustness for both discovery as well as tracking of mutations.  Through unique design and customization, PSS is able to fulfill these requirements.

SafeSeq NGS is a low error rate („safe“) sequencing technology

  • Assignment of a unique identifier (UID) to each DNA molecule to be analyzed
  • Amplification and deep sequencing of universally tagged DNA molecules (UID families)

This allows for differentiation between real mutations and errors introduced during the amplification and sequencing process.

Applications

  • Identification of variants linked to tumor status and drug resistance
  • Mutation analysis of tumor suppressor genes
  • Pathway analysis  

References

 

  1. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Kinde I, Bettegowda C, Wang Y, Wu J, Agrawal N, Shih IeM, Kurman R, Dao F, Levine DA, Giuntoli R, Roden R, Eshleman JR, Carvalho JP, Marie SK, Papadopoulos N, Kinzler KW, Vogelstein B, Diaz LA Jr (2013) Sci Transl. Med. 9;5(167):167ra4.
  2. Detection and quantification of rare mutations with massively parallel sequencing. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B (2011) Proc Natl Acad Sci U S A. 108(23):9530-5. 
  3. Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Wang Y, Li L, Douville C, Cohen JD, Yen TT, Kinde I, Sundfelt K, Kjær SK, Hruban RH, Shih IM, Wang TL, Kurman RJ, Springer S, Ptak J, Popoli M, Schaefer J, Silliman N, Dobbyn L, Tanner EJ, Angarita A, Lycke M, Jochumsen K, Afsari B, Danilova L, Levine DA, Jardon K, Zeng X, Arseneau J, Fu L, Diaz LA Jr, Karchin R, Tomasetti C, Kinzler KW, Vogelstein B, Fader AN, Gilbert L, Papadopoulos N. (2018) Sci Transl Med. 2018 Mar 21;10(433). 
  4. Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Cohen J, Javed AA, Thoburn C, Wong F, Tie J, Gibbs P, Schmidt CM, Yip-Schneider MT, Allen PJ, Schattner M, Brand RE, Singhi AD, Petersen GM, Hong SM, Kim SC, Falconi M, Doglioni C, Weiss MJ, Ahuja N, He J, Makary MA, Maitra A, Hanash SM, Dal Molin M, Wang Y, Li L, Ptak J, Dobbyn L, Schaefer J, Silliman N, Popoli M, Goggins MG, Hruban RH, Wolfgang CL, Klein AP, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Lennon AM. (2017) Proc Natl Acad Sci U S A.114(38):10202-10207.
  5. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Cohen JD, Li L , Wang Y, Thoburn C, Afsari B, Danilova L, Douville C, Javed AA, Wong F, Mattox A, Hruban RH, Wolfgang CL, Goggins MG, Dal Molin M, Wang TL, Roden R, Klein AP, Ptak J, Dobbyn L, Schaefer J, Silliman N, Popoli M, Vogelstein JT, Browne JD, Schoen RE, Brand RE, Tie J, Gibbs P, Wong HL, Mansfield AS, Jen J, Hanash SM, Falconi M, Allen PJ, Zhou S, Bettegowda C, Diaz LA Jr, Tomasetti C, Kinzler KW, Vogelstein B, Lennon AM, Papadopoulos N. (2018) Science. 359(6378):926-930.
  6. Cancer-Associated Mutations in Endometriosis without Cancer. M.S. Anglesio, N. Papadopoulos, A. Ayhan, T.M. Nazeran, M. Noë, H.M. Horlings, A. Lum, S. Jones, J. Senz, T. Seckin, J. Ho, R.-C. Wu, V. Lac, H. Ogawa, B. Tessier-Cloutier, R. Alhassan, A. Wang, Y. Wang, J.D. Cohen, F. Wong, A. Hasanovic, N. Orr, M. Zhang, M. Popoli, W. McMahon, L.D. Wood, A. Mattox, C. Allaire, J. Segars, C. Williams, C. Tomasetti, N. Boyd, K.W. Kinzler, C.B. Gilks, L. Diaz, T.-L. Wang, B. Vogelstein, P.J. Yong, D.G. Huntsman, and I.-M. Shih. (2017) N Engl J Med. 376(19):1835-1848.
  7. Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder. Cowan ML, Springer S, Nguyen D, Taheri D, Guner G, Mendoza Rodriguez MA, Wang Y, Kinde I, Del Carmen Rodriguez Pena M, VandenBussche CJ, Olson MT, Cunha I, Fujita K, Ertoy D, Kinzler K, Bivalacqua T, Papadopoulos N, Vogelstein B, Netto GJ. (2016) Hum Pathol.53:8-13.
  8. High prevalence of TERT promoter mutations in primary squamous cell carcinoma of the urinary bladder. Cowan M, Springer S, Nguyen D, Taheri D, Guner G, Rodriguez MA, Wang Y, Kinde I, VandenBussche CJ, Olson MT, Cunha I, Fujita K, Ertoy D, Bivalacqua TJ, Kinzler K, Vogelstein B, Netto GJ, Papadopoulos N. (2016) Mod Pathol. 29(5):511-5.

 

 

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