Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

Emma Tudini; James Andrews; David M. Lawrence; Sarah L. King-Smith; Naomi Baker; Leanne Baxter; John Beilby; Bruce Bennetts; Victoria Beshay; Michael Black; Tiffany F. Boughtwood; Kristian Brion; Pak Leng Cheong; Michael Christie; John Christodoulou; Belinda Chong; Kathy Cox; Mark R. Davis; Lucas Dejong; Marcel E. Dinger; Kenneth D. Doig; Evelyn Douglas; Andrew Dubowsky; Melissa Ellul; Andrew Fellowes; Katrina Fisk; Cristina Fortuno; Kathryn Friend; Renee L. Gallagher; Song Gao; Emma Hackett; Johanna Hadler; Michael Hipwell; Gladys Ho; Georgina Hollway; Amanda J. Hooper; Karin S. Kassahn; Rahul Krishnaraj; Chiyan Lau; Huong Le; Huei San Leong; Ben Lundie; Sebastian Lunke; Anthony Marty; Mary McPhillips; Lan T. Nguyen; Katia Nones; Kristen Palmer; John V. Pearson; Michael C.J. Quinn; Lesley H. Rawlings; Simon Sadedin; Louisa Sanchez; Andreas W. Schreiber; Emanouil Sigalas; Aygul Simsek; Julien Soubrier; Zornitza Stark; Bryony A. Thompson; James U; Cassandra G. Vakulin; Amanda V. Wells; Cheryl A. Wise; Rick Woods; Andrew Ziolkowski; Marie Jo Brion; Hamish S. Scott; Natalie P. Thorne; Amanda B. Spurdle

doi:10.1016/j.ajhg.2022.10.006

Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

Emma Tudini, James Andrews, David M. Lawrence, Sarah L. King-Smith, Naomi Baker, Leanne Baxter, John Beilby, Bruce Bennetts, Victoria Beshay, Michael Black, Tiffany F. Boughtwood, Kristian Brion, Pak Leng Cheong, Michael Christie, John Christodoulou, Belinda Chong, Kathy Cox, Mark R. Davis, Lucas Dejong, Marcel E. DingerKenneth D. Doig, Evelyn Douglas, Andrew Dubowsky, Melissa Ellul, Andrew Fellowes, Katrina Fisk, Cristina Fortuno, Kathryn Friend, Renee L. Gallagher, Song Gao, Emma Hackett, Johanna Hadler, Michael Hipwell, Gladys Ho, Georgina Hollway, Amanda J. Hooper, Karin S. Kassahn, Rahul Krishnaraj, Chiyan Lau, Huong Le, Huei San Leong, Ben Lundie, Sebastian Lunke, Anthony Marty, Mary McPhillips, Lan T. Nguyen, Katia Nones, Kristen Palmer, John V. Pearson, Michael C.J. Quinn, Lesley H. Rawlings, Simon Sadedin, Louisa Sanchez, Andreas W. Schreiber, Emanouil Sigalas, Aygul Simsek, Julien Soubrier, Zornitza Stark, Bryony A. Thompson, James U, Cassandra G. Vakulin, Amanda V. Wells, Cheryl A. Wise, Rick Woods, Andrew Ziolkowski, Marie Jo Brion, Hamish S. Scott, Natalie P. Thorne, Amanda B. Spurdle

Research output: Contribution to journal › Review article › peer-review

20 Citations (Scopus)

Abstract

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

Original language	English
Pages (from-to)	1960-1973
Number of pages	14
Journal	American Journal of Human Genetics
Volume	109
Issue number	11
DOIs	https://doi.org/10.1016/j.ajhg.2022.10.006
Publication status	Published - 3 Nov 2022

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10.1016/j.ajhg.2022.10.006

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Tudini, E., Andrews, J., Lawrence, D. M., King-Smith, S. L., Baker, N., Baxter, L., Beilby, J., Bennetts, B., Beshay, V., Black, M., Boughtwood, T. F., Brion, K., Cheong, P. L., Christie, M., Christodoulou, J., Chong, B., Cox, K., Davis, M. R., Dejong, L., ... Spurdle, A. B. (2022). Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation. American Journal of Human Genetics, 109(11), 1960-1973. https://doi.org/10.1016/j.ajhg.2022.10.006

@article{4391465070154f06a70ceadd79fad507,

title = "Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation",

abstract = "Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.",

author = "Emma Tudini and James Andrews and Lawrence, {David M.} and King-Smith, {Sarah L.} and Naomi Baker and Leanne Baxter and John Beilby and Bruce Bennetts and Victoria Beshay and Michael Black and Boughtwood, {Tiffany F.} and Kristian Brion and Cheong, {Pak Leng} and Michael Christie and John Christodoulou and Belinda Chong and Kathy Cox and Davis, {Mark R.} and Lucas Dejong and Dinger, {Marcel E.} and Doig, {Kenneth D.} and Evelyn Douglas and Andrew Dubowsky and Melissa Ellul and Andrew Fellowes and Katrina Fisk and Cristina Fortuno and Kathryn Friend and Gallagher, {Renee L.} and Song Gao and Emma Hackett and Johanna Hadler and Michael Hipwell and Gladys Ho and Georgina Hollway and Hooper, {Amanda J.} and Kassahn, {Karin S.} and Rahul Krishnaraj and Chiyan Lau and Huong Le and {San Leong}, Huei and Ben Lundie and Sebastian Lunke and Anthony Marty and Mary McPhillips and Nguyen, {Lan T.} and Katia Nones and Kristen Palmer and Pearson, {John V.} and Quinn, {Michael C.J.} and Rawlings, {Lesley H.} and Simon Sadedin and Louisa Sanchez and Schreiber, {Andreas W.} and Emanouil Sigalas and Aygul Simsek and Julien Soubrier and Zornitza Stark and Thompson, {Bryony A.} and James U and Vakulin, {Cassandra G.} and Wells, {Amanda V.} and Wise, {Cheryl A.} and Rick Woods and Andrew Ziolkowski and Brion, {Marie Jo} and Scott, {Hamish S.} and Thorne, {Natalie P.} and Spurdle, {Amanda B.}",

note = "Funding Information: The authors would like to thank Penny Glenn, who led the development of the Shariant terms of use and multiple rounds of minor amendments in consultation with laboratory legal teams. We also thank the laboratories who participated in the landscape analysis in 2017 and all individuals who attended the Human Genetics Society of Australasia conference workshop. We thank John Rowell and Valentine Hyland for their prior contributions to engagement of Pathology Queensland and the GenoVic team for efforts relating to initial integration of GenoVic laboratories. We wish to acknowledge Agilent Technologies, for its contribution of technical resources and ongoing support to achieve interoperability of Shariant with Agilent's variant tertiary analysis system. Shariant Australia (including funding for E.T. and J.A.) is supported by Australian Genomics (NHMRC grants GNT1113531 and GNT2000001). A.B.S was supported by NHMRC fellowship funding (APP1061779, APP177524). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. Hosting of Shariant on Amazon Web Services between October 2018 and September 2019 was supported by an Amazon Web Services Cloud Credit for Research grant. The authors declare no competing interests. Funding Information: The authors would like to thank Penny Glenn, who led the development of the Shariant terms of use and multiple rounds of minor amendments in consultation with laboratory legal teams. We also thank the laboratories who participated in the landscape analysis in 2017 and all individuals who attended the Human Genetics Society of Australasia conference workshop. We thank John Rowell and Valentine Hyland for their prior contributions to engagement of Pathology Queensland and the GenoVic team for efforts relating to initial integration of GenoVic laboratories. We wish to acknowledge Agilent Technologies, for its contribution of technical resources and ongoing support to achieve interoperability of Shariant with Agilent{\textquoteright}s variant tertiary analysis system. Shariant Australia (including funding for E.T. and J.A.) is supported by Australian Genomics ( NHMRC grants GNT1113531 and GNT2000001 ). A.B.S was supported by NHMRC fellowship funding ( APP1061779 , APP177524 ). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program . The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation . Hosting of Shariant on Amazon Web Services between October 2018 and September 2019 was supported by an Amazon Web Services Cloud Credit for Research grant. Publisher Copyright: {\textcopyright} 2022 American Society of Human Genetics",

year = "2022",

month = nov,

day = "3",

doi = "10.1016/j.ajhg.2022.10.006",

language = "English",

volume = "109",

pages = "1960--1973",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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number = "11",

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Tudini, E, Andrews, J, Lawrence, DM, King-Smith, SL, Baker, N, Baxter, L, Beilby, J, Bennetts, B, Beshay, V, Black, M, Boughtwood, TF, Brion, K, Cheong, PL, Christie, M, Christodoulou, J, Chong, B, Cox, K, Davis, MR, Dejong, L, Dinger, ME, Doig, KD, Douglas, E, Dubowsky, A, Ellul, M, Fellowes, A, Fisk, K, Fortuno, C, Friend, K, Gallagher, RL, Gao, S, Hackett, E, Hadler, J, Hipwell, M, Ho, G, Hollway, G, Hooper, AJ, Kassahn, KS, Krishnaraj, R, Lau, C, Le, H, San Leong, H, Lundie, B, Lunke, S, Marty, A, McPhillips, M, Nguyen, LT, Nones, K, Palmer, K, Pearson, JV, Quinn, MCJ, Rawlings, LH, Sadedin, S, Sanchez, L, Schreiber, AW, Sigalas, E, Simsek, A, Soubrier, J, Stark, Z, Thompson, BA, U, J, Vakulin, CG, Wells, AV, Wise, CA, Woods, R, Ziolkowski, A, Brion, MJ, Scott, HS, Thorne, NP & Spurdle, AB 2022, 'Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation', American Journal of Human Genetics, vol. 109, no. 11, pp. 1960-1973. https://doi.org/10.1016/j.ajhg.2022.10.006

TY - JOUR

T1 - Shariant platform

T2 - Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

AU - Tudini, Emma

AU - Andrews, James

AU - Lawrence, David M.

AU - King-Smith, Sarah L.

AU - Baker, Naomi

AU - Baxter, Leanne

AU - Beilby, John

AU - Bennetts, Bruce

AU - Beshay, Victoria

AU - Black, Michael

AU - Boughtwood, Tiffany F.

AU - Brion, Kristian

AU - Cheong, Pak Leng

AU - Christie, Michael

AU - Christodoulou, John

AU - Chong, Belinda

AU - Cox, Kathy

AU - Davis, Mark R.

AU - Dejong, Lucas

AU - Dinger, Marcel E.

AU - Doig, Kenneth D.

AU - Douglas, Evelyn

AU - Dubowsky, Andrew

AU - Ellul, Melissa

AU - Fellowes, Andrew

AU - Fisk, Katrina

AU - Fortuno, Cristina

AU - Friend, Kathryn

AU - Gallagher, Renee L.

AU - Gao, Song

AU - Hackett, Emma

AU - Hadler, Johanna

AU - Hipwell, Michael

AU - Ho, Gladys

AU - Hollway, Georgina

AU - Hooper, Amanda J.

AU - Kassahn, Karin S.

AU - Krishnaraj, Rahul

AU - Lau, Chiyan

AU - Le, Huong

AU - San Leong, Huei

AU - Lundie, Ben

AU - Lunke, Sebastian

AU - Marty, Anthony

AU - McPhillips, Mary

AU - Nguyen, Lan T.

AU - Nones, Katia

AU - Palmer, Kristen

AU - Pearson, John V.

AU - Quinn, Michael C.J.

AU - Rawlings, Lesley H.

AU - Sadedin, Simon

AU - Sanchez, Louisa

AU - Schreiber, Andreas W.

AU - Sigalas, Emanouil

AU - Simsek, Aygul

AU - Soubrier, Julien

AU - Stark, Zornitza

AU - Thompson, Bryony A.

AU - U, James

AU - Vakulin, Cassandra G.

AU - Wells, Amanda V.

AU - Wise, Cheryl A.

AU - Woods, Rick

AU - Ziolkowski, Andrew

AU - Brion, Marie Jo

AU - Scott, Hamish S.

AU - Thorne, Natalie P.

AU - Spurdle, Amanda B.

N1 - Funding Information: The authors would like to thank Penny Glenn, who led the development of the Shariant terms of use and multiple rounds of minor amendments in consultation with laboratory legal teams. We also thank the laboratories who participated in the landscape analysis in 2017 and all individuals who attended the Human Genetics Society of Australasia conference workshop. We thank John Rowell and Valentine Hyland for their prior contributions to engagement of Pathology Queensland and the GenoVic team for efforts relating to initial integration of GenoVic laboratories. We wish to acknowledge Agilent Technologies, for its contribution of technical resources and ongoing support to achieve interoperability of Shariant with Agilent's variant tertiary analysis system. Shariant Australia (including funding for E.T. and J.A.) is supported by Australian Genomics (NHMRC grants GNT1113531 and GNT2000001). A.B.S was supported by NHMRC fellowship funding (APP1061779, APP177524). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. Hosting of Shariant on Amazon Web Services between October 2018 and September 2019 was supported by an Amazon Web Services Cloud Credit for Research grant. The authors declare no competing interests. Funding Information: The authors would like to thank Penny Glenn, who led the development of the Shariant terms of use and multiple rounds of minor amendments in consultation with laboratory legal teams. We also thank the laboratories who participated in the landscape analysis in 2017 and all individuals who attended the Human Genetics Society of Australasia conference workshop. We thank John Rowell and Valentine Hyland for their prior contributions to engagement of Pathology Queensland and the GenoVic team for efforts relating to initial integration of GenoVic laboratories. We wish to acknowledge Agilent Technologies, for its contribution of technical resources and ongoing support to achieve interoperability of Shariant with Agilent’s variant tertiary analysis system. Shariant Australia (including funding for E.T. and J.A.) is supported by Australian Genomics ( NHMRC grants GNT1113531 and GNT2000001 ). A.B.S was supported by NHMRC fellowship funding ( APP1061779 , APP177524 ). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program . The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation . Hosting of Shariant on Amazon Web Services between October 2018 and September 2019 was supported by an Amazon Web Services Cloud Credit for Research grant. Publisher Copyright: © 2022 American Society of Human Genetics

PY - 2022/11/3

Y1 - 2022/11/3

N2 - Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

AB - Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

UR - http://www.scopus.com/inward/record.url?scp=85140999484&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2022.10.006

DO - 10.1016/j.ajhg.2022.10.006

M3 - Review article

C2 - 36332611

AN - SCOPUS:85140999484

SN - 0002-9297

VL - 109

SP - 1960

EP - 1973

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 11

ER -

Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

Abstract

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Australian Genomics 2.0

Preparing Australia for Genomic Medicine - A proposal by the Australian Genomics Health Alliance

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Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation

Abstract

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Projects

Australian Genomics 2.0

Preparing Australia for Genomic Medicine - A proposal by the Australian Genomics Health Alliance

Cite this