Cancer genomics is one of the most complex and consequential areas in all of life sciences. The genetic and epigenetic changes that drive tumor development, progression, and treatment resistance are often too intricate for any single technology to fully capture. HiFi long-read sequencing changes that and is precisely why this year’s long-read cancer multiomics SMRT Grant drew such compelling proposals. Researchers are eager for tools that can see more, and do more, in a single experiment.
We’re excited to announce the winner of the 2026 long-read cancer multiomics SMRT Grant and to spotlight the finalists whose work exemplifies the breadth of cancer research being advanced by long-read sequencing.
Announcing the 2026 winner
Yanding Zhao – Mohamed Bin Zayed University of Artificial Intelligence
Long-read sequencing to decipher non-canonical homologous recombination deficiency (HRD) mechanisms and structural variants in high-risk osteosarcoma
High-risk osteosarcoma patients often exhibit an “HRD-like” phenotype characterized by genomic instability and poor chemotherapy response, yet they lack canonical BRCA1/2 mutations. Our preliminary data shows these tumors are sensitive to PARP inhibitors and exhibit reduced BRCA1 promoter accessibility, suggesting epigenetic silencing. Leveraging PacBio SMRT sequencing, we will integratedly profile DNA methylation and large-scale tandem duplications to validate BRCA1 hypermethylation as a driver of this non-canonical HRD. Furthermore, we will explore how these structural rearrangements disrupt or amplify regulatory elements. This study aims to provide a definitive molecular basis for stratifying and treating high-risk, HRD-like osteosarcoma.
Recognizing our finalists
Landry Nfonsam – Hamilton Health Sciences, McMaster University
Integrating PacBio HiFi long-read sequencing into clinical cancer genomics and precision drug discovery at Hamilton Health Sciences, Canada
PacBio HiFi Single Molecule Real-Time long-read sequencing can overcome limitations associated with conventional short-read sequencing and cytogenetic testing in cancer genomics. We plan to use this technology to evaluate detection of clinically relevant structural and sequence-level variants, identify novel genomic rearrangements with potential drug-discovery relevance, assess reductions in sequential testing burden, and determine feasibility for routine clinical implementation within the HHS Clinical Genetics Diagnostic Laboratory. Representative hereditary cancer, cytogenetic, myeloid malignancy, and leukemia fusion samples will undergo HiFi sequencing and comparison with current standard-of-care methodologies. Long-read sequencing is expected to improve genomic resolution, workflow efficiency, precision oncology applications, and biomarker discovery.
My Hoang – Washington University in Saint Louis
Long-read multiomics reveals the true neoantigen landscape for personalized cancer vaccine development
Personalized cancer vaccines depend on accurate neoantigen prediction, yet short-read RNA sequencing falls short in two key ways. First, computationally assembled transcripts from short reads may be artifacts, making it challenging to identify true novel isoforms. Second, short-read cannot resolve which transcript isoform carries a somatic mutation of interest, risking therapy manufacturing on the wrong protein sequence. Using preliminary solid tumor data, we compare neoantigen landscapes from short- vs long-read RNA sequencing. PacBio HiFi full-length isoform sequencing eliminates transcript assembly guesswork, pinpointing the exact protein produced by each expressed mutation, directly enabling the development of better personalized vaccines for patients.
Christina Piperi – National Kapodistrian University of Athens
Long-read multiomic profiling of WDR5 inhibition in pediatric glioma using PacBio HiFi sequencing
Pediatric high-grade gliomas are aggressive brain tumors driven in part by epigenetic dysregulation. This project will use PacBio HiFi long-read sequencing to profile transcriptomic and epigenetic changes in SJ-GBM2 and CHLA-200 pediatric glioma cell lines treated with WDR5 inhibitors. HiFi sequencing enables accurate detection of full-length transcript isoforms, alternative splicing, structural variants, and regulatory genomic regions that are difficult to resolve with short-read technologies. By integrating multiomic datasets, we aim to identify disrupted oncogenic pathways, biomarkers of therapeutic response, and chromatin-associated mechanisms driving glioma progression, supporting the development of precision epigenetic therapies for pediatric brain tumors.
Che Kang Lim – Singapore General Hospital
Integrating long-read multiomic sequencing to decode the genomic and epigenetic progression of nasopharyngeal carcinoma
PacBio HiFi DNA sequencing provides a multiomic layer by simultaneously capturing genetic and epigenetic alterations in a single run. Combined with existing long-read RNA-seq data, it enables precise tracking of molecular transitions from early- to late-stage nasopharyngeal carcinoma (NPC): A) Epigenetic Shifts: Direct, native 5mC methylation calling maps progressive tumor suppressor silencing or oncogene activation without bisulfite bias. B) Structural Variation: Long, highly accurate reads resolve copy number variations, complex genomic rearrangements and chromosomal breakpoints driving metastasis. C) Viral Dynamics: It potentially maps somatic Epstein-Barr virus (EBV) integration sites, revealing how viral-host interactions drive tumor evolution and stage progression.
About the PacBio Grant Program
The PacBio Grant Program provides researchers anywhere in the world access to complimentary PacBio sequencing for genomics projects across a wide range of applications. To apply, researchers choose an active grant program aligned with their work and submit a short proposal describing how HiFi sequencing will advance their research.
Selected winners receive free sequencing services, which can include consumables, library preparation, and preliminary bioinformatic analyses, all provided by an authorized sequencing service provider (terms and conditions apply). Grant opportunities span research areas from oncology and rare disease to biodiversity and microbiology.
A sincere thank-you to everyone who submitted a proposal this year. The creativity and rigor behind these applications, winner and finalists alike, reflect how much is possible when researchers have access to the right sequencing tools. Keep an eye on the PacBio Grant Program page for upcoming opportunities.