Long Read Sequencing2

In March 2024, PRECISE launched an open Call for Sample Submission for Long-read Sequencing. This initiative invited Singapore-based researchers to submit proposals for sequencing human genomic DNA samples using PacBio's SMRT cells.

The Evaluation Committee selected four projects that showcased the value of long-read sequencing in genetics and diagnosis, and novel applications to improve population health.

S/N	Project Title	Team	Aims of Project
1	Long read sequencing study of undiagnosed genetic adult neuromuscular disease whereby short read sequencing did not result in a molecular diagnosis Topic: Neuromuscular disorder	Lead PI: Dr Chen Zhiyong, National Neuroscience Institute Co-Lead PI: Dr Kaavya Narasimhalu, National Neuroscience Institute Co-Lead PI: Dr Lim Weng Khong, Duke-NUS Medical School	1. Investigate the genetic basis for neuromuscular diseases amongst patients who did not get a molecular diagnosis through short read sequencing. 2. Uncover novel variants that may contribute to the development of neuromuscular disease. 3. Collaborate with international collaborators to functionally confirm the potential molecular findings.
2	Characterising the genetic mutational burden and effects on disease outcomes in Singapore Interstitial Lung Diseases (ILD) patients Topic: Lung disease	Lead PI: Dr Kam Li Wei Michelle, Singapore General Hospital Co-Lead PI: A/P Joanne Ngeow, Lee Kong Chian School of Medicine, NTU	1. Uncover gene mutations that correlate with aggressive disease behavior in Singapore ILD patients.
3	Identification of noncoding founder mutations in Singaporeans with Inherited Retinal Degeneration (IRD) Topic: Retinal disease	Lead PI: Dr Beau J. Fenner, Singapore National Eye Centre Co-Lead PI: Dr Chan Choi Mun, Singapore National Eye Centre Co-Lead PI: Dr Saumya Jamuar, Duke-NUS Medical School	1. Identify noncoding founder mutations that cause inherited retinal diseases in Singapore.
4	Long-read whole genome sequencing of gastric cancer cell lines and organoids Topic: Gastric cancer	Lead PI: Prof Patrick Tan, Duke-NUS Medical School	1. Perform comprehensive mapping of the DNA mutation, methylation and structural variation landscape across cell lines and organoids derived from normal stomach, intestinal metaplasia (IM), primary and metastatic gastric cancers (GC). 2. Identify subtype-specific novel genetic/epigenetic drivers and risk markers for GC initiation and progression. 3. Evaluate biological mechanisms governing GC development from normal stomach to IM and from primary to metastatic GC.