What Is Next-Generation Genome Sequencing?

As we move further into the 21^st century, the ways in which oncologists diagnose and treat cancer are rapidly evolving. Traditionally, cancer treatment plans were developed based on a limited set of clinical factors, such as the type and stage of a tumor. Although this approach has extended and saved countless lives over the course of decades, the efficacy of such treatments is limited because they are targeted to an average population rather than specific individuals. As researchers gained a deeper understanding of the genomic and molecular underpinnings of specific types of cancers, it became clear that targeted therapy was the future of cancer care. Indeed, creating personalized therapies around the genetic characteristics of individual patients’ tumors is already beginning to revolutionize the way we treat cancer.

Next-generation sequencing (NGS) has an essential role to play in making targeted therapy the standard of cancer care. Also called massive parallel sequencing, this set of technologies has dramatically improved the speed and scalability of genome sequencing when compared to previous techniques. While still a fledgling technology, next-generation sequencing has become an incredibly powerful tool for researchers worldwide, including the oncology-focused bioinformatics specialists at M2GEN.

The Evolution of Next-Generation Sequencing
DNA sequencing has been used for decades, originating in the late 1970s with researcher Frederick Sanger, who innovated the chain-termination sequencing method. This method was refined and automated in the ensuing decades, eventually allowing for the Human Genome Project to achieve the first complete mapping of the human genome in 2003. This milestone opened a wide array of research avenues in oncology and was critical in advancing the understanding of cancer as a genetic disease. However, the techniques used were extremely time and cost intensive, thereby limiting their clinical application.

Next-generation sequencing is changing this. The approach used in modern sequencing technologies is fundamentally different than that used in previous generations. Specifically, instead of chain termination, next-generation techniques involve parallel analysis along with ultra-high throughput, allowing for faster, deeper analysis at a relatively low cost. For example, whereas it took an international consortium billions of dollars and more than a decade to develop the first whole-genome sequence, next-generation sequencing can provide results with much greater resolution in a matter of days. These revolutionary techniques and technologies are becoming commonplace research tools.

Next-Generation Sequencing in the Fight Against Cancer
Researchers have developed an understanding of cancer as a genetic illness caused by somatically acquired mutations. In the effort to bring about a revolution in personalized cancer management, next-generation sequencing will be key both in furthering researchers’ understanding of the genetic changes that cause cancer and in helping them develop treatments that target such mutations.

The capacity of next-generation sequencing to provide an efficient, systemic study of entire cancer genomes has led to its adoption by large-scale cancer genomics projects around the world. Today, modern sequencing techniques are helping scientists identify rare cancer mutations, classify familial mutations, and isolate actionable cancer biomarkers that are candidates for newly developed treatments. However, researchers still need to overcome significant challenges to make next-generation sequencing a standard part of individual patient cancer care. For example, as sequencing technologies evolve, the goals are to simplify assays, shorten turnaround times, reduce costs, and allow for greater sensitivity and throughput flexibility. Additionally, to make sense of the vast quantities of data that genetic sequencing produces, bioinformatics specialists will need to increase the efficiency and precision of data analysis and interpretation. At M2GEN, we’re taking this challenge head on.

How M2GEN Leverages Next-Generation Genome Sequencing
At M2GEN, our Bioinformatics Support Services team has established a standardized, best-in-class next-generation sequencing analysis pipeline, which can include:

• Tumor-Only RNA Sequencing (RNA-Seq T-Only) analysis
• Tumor-Only Whole Exome Sequencing (WES T-Only) analysis with Virtual Normal (VN) somatic mutation classification
• Paired Tumor and Germline Whole Exome Sequencing (WES T/G) analysis with Panel of Normals (PoN) filtering

To ensure our partners in academia and biopharmaceutical industries receive the most accurate analyses possible, we utilize one of the largest PoNs available for somatic mutation calling. This includes more than 20,000 germline samples to inform the segregation of somatic and germline variants to accurately identify recurrent sequencing artifacts. Additionally, we leverage up-to-date human genome reference (GRCh38/hg38) and gene build (Gencode V32) to ensure our pipeline analysis is WES and RNA-Seq capture kit agnostic.

Our bioinformatics solutions are designed for large-scale oncology and multi-omics research. In addition to molecular data from next-generation exome and RNA sequencing, our solutions include robust clinical information, providing complete pictures of different cancer types and clear insights into highly specific patient cohorts. From the discovery of actionable cancer biomarkers to the development of effective clinical trials, M2GEN’s bioinformatics tools and services allow researchers to dedicate more resources to discovery and less to data generation, analysis, and interpretation.

At M2GEN, we believe next-generation genome sequencing will continue to bring about invaluable insights in the effort to make personalized cancer management a reality for millions of patients worldwide. Contact us today to learn more about how our bioinformatics and computational biology experts are making the most of modern sequencing techniques and technologies to advance the study and treatment of cancer.