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[42]
standards and guidelines of the American College of Medical Genetics (ACMG) . Post-analysis
multidisciplinary team (MDT) meetings facilitate the exchange of views on the GS findings with respect to
patient clinical indications, refining diagnoses and clinical management plans for individual patients. GS
findings are validated by appropriate orthogonal methods such as Sanger sequencing, RNA sequencing,
long-read sequencing, and digital PCR.

RESULTS
Hong Kong genome institute laboratory
Taking references and guidelines from various professional bodies into consideration, the development of
the laboratory data information management system and GS workflow is fine-tuned to meet the
recommendations set out by the Medical Genome Initiative for clinical GS [43-46] . One of the critical features
of the Laboratory design is the capability of conducting a unidirectional workflow, and in conjunction with
proper laboratory practices and operation, can minimise the risk of sample contamination. It requires
physical separation of different stages of the procedure, dedicated equipment and supplies for each stage,
and a workflow that prevents samples or laboratory personnel from moving “backwards” to potentially
contaminate upstream workspaces [Figure 2]. In addition, differential air pressure is maintained to prevent
contamination between the rooms. Pass-through chambers with interlocking doors and UV sterilisation
capability enable the transfer of reagents or samples between physically separated rooms without
compromising isolation and minimising cross-contamination. It ensures that reagents and samples pass
through the Laboratory according to the designated route as demarcated in the GS workflow. Briefly, the GS
workflow is divided into six wet-bench processes, in the order of: (i) reagent preparation; (ii) biological
sample reception and registration; (iii) sample processing and biobanking; (iv) nucleic acid extraction; (v)
GS library preparation and quality assessment; and (vi) sequencing. The main steps are performed in six key
rooms, including the Reagent Preparation Room, Sample Reception Room, Sample Processing Room,
Freezer/Biobank Room, Library Preparation Room, and Sequencing Room [Figure 2].
[47]
The Hong Kong genome project biobank
HKGI developed and employed the data manager, Clinical FrontEnd, to facilitate and standardise the
patient recruitment process and clinical data collection across different recruitment sites, by properly
handling and housing different types of data from the participants [Figure 3]. The interface of this portal
includes an e-consent form and a clinical information collection form for supporting patient recruitment,
while the specimen collection form and GS report provide efficient information exchange between the
HKGI and PCs. The participants’ samples are collected at the PCs, and then delivered to the HKGI
Laboratory, which acts as a central processing hub for registration, processing, and biobanking. After
verification of the participant’s identification data in the Clinical FrontEnd, the samples are de-identified to
protect participants’ personal data and confidentiality, and a HKGI Laboratory ID, a unique alphanumeric
identifier, is assigned for downstream processing [Figure 3]. The de-identified HKGI Laboratory IDs are
handed over to the LabKey Sample Manager, which is an independent environment for handling laboratory
data generated from the HKGP samples and biobank. Its logical data structure, fine-grained security
management of data access, and intuitive user-friendly interface facilitate the tracking of samples and
reagents in the Laboratory [Figure 3].

The Laboratory routinely handles and analyses approximately 350-500 samples per week of various natures
ranging from whole blood, buccal swab, saliva, and tissues. Sample processing uses a hybrid of manual and
automated approaches; details of the operations such as date and time, operator identifiers, and location are
logged in the Sample Manager system. To minimise repeated freeze-thaw cycles and potential sample
degradation and contamination, samples are first divided into aliquots, barcoded, and transferred to the
ultra-low temperature archives of the HKGP biobank [Figure 3]. The system maintains audit logs