At the Advances in Genome Biology and Technology general meeting, innovators from industry and academia discuss how recent advances in whole genome sequencing are propelling cancer research.
Complete Genomics’ DNBSEQ-T20×2 Sequencer/courtesy of Complete Genomics
Precision oncology has been a game-changer for a small number of cancer patients, but there is much potential still left on the table. Recent advances in whole genome sequencing (WGS) could bring these medicines to many more people.
At the Advances in Genome Biology and Technology (AGBT) general meeting, Feb. 6-9, innovators from industry and academia will discuss recent advances in WGS and how to best leverage them for diagnostic and therapeutic purposes. Several abstracts will focus on applications in oncology.
Genome-targeted therapies are prescribed based on aberrations identified in a genomic test. As of 2018, the FDA had approved 28 such therapies for cancer. The same year, investigators writing in Targeted Oncology predicted that 8.3% of patients were eligible for genomic-targeted therapy – of which just 4.9% were likely to respond. Another paper, published in Nature in 2020, put this number at 5 to 10%.
Genes - of which there are up to 25,000 in the human body - are intricately involved in the development of tumors.
DNA sequencing can identify single-nucleotide variants, insertions, deletions, copy number changes and fusions that may drive cancer growth.
Access Equals Knowledge
In recent years, the cost of WGS has fallen from more than $1000 per genome to the hundred-dollar range. On Feb 7 at AGBT, California-based Complete Genomics, a subsidiary of MGI Tech, introduced DNBSEQ-T20×2, which reduces the cost of personal WGS to under $100. The product, which can sequence more than 50,000 human genomes per year at 30x read coverage and high DNBSEQ quality, will be available in the U.S. in Q3, 2023.
Affordable WGS enables individuals to sequence their inherited genomes for genetic mutations such as BRCA1 or BRCA2 – mutations particularly implicated in breast and ovarian cancers.
Tools like DNBSEQ-T20×2 enable both physicians and researchers to conduct deeper sequencing of cancerous tissues and cell-free DNA (cfDNA).
“Cell-free DNA is very informative to screen for noninvasive early cancer detection,” Rade Drmanac, Ph.D., chief scientific officer, Complete Genomics, told BioSpace.
This is because tumor-specific genomic alterations can be identified in cfDNA from patient blood samples. For oncologists, this can enable real-time molecular monitoring of a given therapy, detection of recurrence, and insights into resistance.
High throughput sequencing also enables physicians to monitor gene expression in the immune cells. There are more than 60 subtypes of single cells, and technology such as Complete Genomics’ DNBSEQ allows researchers to identify a single subtype that may not be behaving normally, Drmanac said.
When a patient is diagnosed with cancer, efficiency is of the essence.
To this end, Complete Genomics introduced DNBSEQ-G99, which the company dubbed ‘the King of Speed.’”
DNBSEQ-G99 adopts triangular matrix signal spots on sequencing flow cells, enabling it to reach a higher density of data output and a shortened PE150 data sequencing turn-around time of less than 12 hours. This allows the user to sequence panels for mutations that could inform the correct course of treatment.
Propelling Cancer Research
Many presentations at AGBT will focus on leveraging efficient DNA sequencing for research purposes.
At Stanford University, Hanlee P. Ji, M.D., associate professor of medicine, focuses his research on cancer genetics. A key project involves explaining the genetic mechanisms and biology underlying the metastatic spread of cancers.
On Feb. 6th, Ji presented an abstract entitled “Single-cell discovery of cancer point mutations and rearrangements with adaptive nanopore sequencing of transcripts”.
The proof-of-concept study demonstrates how researchers can reconstruct features to identify mutation rearrangements and transcript isoforms using standard single-cell RNA sequencing.
“One of the most important features was the fact that you can do multiple overlapping, long read and short read analysis from the same set of single cells,” Ji told BioSpace.
He credited this to the recent advances in nanopore sequencing, which he said has reached a level of accuracy and outputs that it is practical to do multi-omic integrated studies on any type of single-cell analysis, including primary tumors.
Spatial transcript Omics technology, such as STOmics, provides subcellular resolution so researchers can more deeply mine gene expression in a tissue sample at an affordable price using DNBSEQ-T7 or DNBSEQ-T20 sequencers. This enables researchers to identify “where…a given gene is expressed, which cell, and where within the cell,” Drmanac said.
What to Watch for at AGBT
At AGBT, Ji will keep an eye on sessions hosted by his Stanford colleagues.
On Feb. 6, Billy Lau, Ph.D., an instructor at the Stanford School of Medicine, gave a plenary talk on cell-free detection of breast cancer based upon DNA methylation profiling. And on Feb. 8, Ji’s post-doc student Heonseok Kim, Ph.D., will discuss single-cell modeling and phenotyping of cancer mutations with transcript-informed CRISPR engineering.
For his part, Drmanac is interested in learning about “the other enablers” of WGS use – namely, bioinformatics and analytics tools, which he said enable a better understanding and interpretation of the genome.
“Without that, there is no genome sequencing.”
