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Chu et al. J Transl Genet Genom 2023;7:196-212 https://dx.doi.org/10.20517/jtgg.2023.22 Page 100

recommendations for the strategic development of genomic medicine in Hong Kong, including the set-up
of the Hong Kong Genome Institute (HKGI) in 2020 under the Health Bureau, to implement the Hong
[34]
Kong Genome Project (HKGP) in 2021 . HKGP is the first large-scale GS project in the city to catapult
[34]
genetic and genomic services and research , marking an important milestone in the revolution of the
healthcare system in Hong Kong [7,27] . Accelerating the advancement of genomic medicine, HKGP is
conducted in two phases: the pilot phase and the main phase. In the pilot phase, from mid-2021 to late 2022,
efforts were dedicated to developing and streamlining operational workflows for genomic diagnosis, with
the aim to sequence and analyse approximately 5,000 genomes by GS to demonstrate the capability of HKGI
and the feasibility of HKGP [7,27] . This represents approximately 2,000 cases of patients with undiagnosed
diseases or hereditary cancers and their family members, with the majority of the cases subjected to trio
analysis to assist in genomic data interpretation. Valuable experience and insights gained from the pilot
phase have laid a solid foundation for formulating directions for the main phase, adding “genomics and
precision health” as a new theme, covering other disease and research cohorts, and aiming to sequence
45,000-50,000 genomes (approximately 18,000-20,000 cases) over three years from 2023 to 2025 .
[34]
The entire patient journey is the highlight of HKGP, with considerable efforts dedicated to designing and
crafting the protocol and process according to international standards of medical ethics and participants’
[7]
rights . According to the advice sought from the various professional bodies and personnel, this patient-
centered process starts with clinician engagement, and the emphasis that all personnel are fully aware of the
importance of a thorough informed consent process. Another primary and unique process is the element of
genetic counselling. To facilitate the implementation of HKGP through addressing the needs and challenges
of the profession, a representative group of experts and stakeholders in the fields of genetics and genomics
was gathered to standardise genomic counselling practice. While pre-test genetic counselling focuses on the
process of translating complex genetic information into colloquial and relevant information between the
clinicians and the patient, post-test genetic counselling provides an opportunity for participants to
understand the genetic diagnosis and discuss the implications of the findings with genetic counsellors or
clinical geneticists. The project also has clear protocols for withdrawal procedures, in which withdrawal
does not preclude joining the project again, for re-enrollment and consenting procedures were addressed in
the project design.

For a seamless GS operation at the beginning of the HKGP, a sequencing service provider was engaged to
provide the wet-lab process while the HKGI laboratory was designed and built to provide a bespoke GS
workflow with a laboratory information management system. To handle the increasing workload and tight
timeline, a NovaSeq 6000 was installed in the HKGI laboratory in mid-2022 to boost the sequencing
capacity for the project. A bioinformatics pipeline and variant curation workflow were also developed to
assist in the identification of causal variants. Multidisciplinary team (MDT) meeting is an integral part of
the HKGP, allowing exchanges from relevant specialists to attain consensus on a molecular diagnosis and
clinical management plan. By leveraging the collective knowledge and skills of different specialties, such as
clinicians, genetic counsellors, laboratory scientists, genome curators, bioinformaticians, allied health
professionals, and trainees, HKGP has been tackling complex genomic challenges and delivering cutting-
edge advancements in healthcare. This collaborative environment allows for prime integration of diverse
expertise and perspectives, fostering innovative approaches and ensuring comprehensive patient care.

The present paper focuses on sharing the experience in setting up the HKGI laboratory and genome
sequencing workflow, and scaling up the sequencing capability and capacity in the laboratory to handle the
increasing workload for the HKGP. The HKGI laboratory (Laboratory) comprises four major components:
(i) multidisciplinary talents; (ii) laboratory infrastructure tailored for clinical genomics; (iii) scalable semi-