Los Angeles, CA September 1, 2016 – In recent years, sequencing technologies have advanced incredibly quickly, and sequencing costs have plummeted from millions of dollars to a mere thousand dollars per genome. As the accessibility and power of sequencing technologies have increased, it is now widely accepted that using next generation sequencing (NGS) to diagnose and to assist therapy choice and treatment monitoring for patients will become routine procedure.We conducted a review of 1,200 randomly selected peer-reviewed publications using clinical samples, and observed an increasing use of NGS in a broad variety of therapeutic areas. Within these publications, approximately a third are within oncology, and targeted sequencing is the most common application both across all focus areas and within oncology.Click on each category (i.e. Oncology, Targeted Sequencing) in the interactive Tableau™ dashboard below to filter the results. Click on the same category again to clear filter, or use Ctrl + click to make multiple selections.

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To investigate whether these trends are also reflected in clinical trials, I focused on the subset of trials on clinicaltrials.gov searching for the term “next generation sequencing”. Within the 163 clinical trials identified, the general trend from 2009 shows increasing clinical studies using NGS. When grouping trials by conditions, we also see that the majority of NGS clinical trials address oncology (neoplasms). Although there appears to be a dip in number of oncology-related studies in 2015, the 3 trial decrease from the previous year is inconclusive, due to the small sample size, and overall, NGS usage in oncology appears to be on the rise.In order to gather further qualitative insights into current and future trends in the clinical NGS landscape, the team at DeciBio recently interviewed 30 NGS key opinion leaders, and the information gleaned from these interviews will be summarized in a poster presentation at the Advances in Genome Biology and Technology (AGBT) conference in Arizona this month. Based on these interviews and other analyses, here is a selection of trends that we expect to see in the clinical landscape:

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Liquid biopsies will play an increasing role in tackling cancer, but will be used in addition to rather than instead of solid tumor testing. Currently, a big portion of NGS clinical activity is for liquid biopsies in non-invasive prenatal testing (NIPT), a non-invasive alternative to amniocentesis that entails analyzing the circulating fetal DNA in maternal blood to screen for chromosomal abnormalities. In oncology, liquid biopsies may follow a similar trend to becoming a less invasive alternative to solid tumor testing, especially in cancers for which it is dangerous or difficult to obtain a sufficient number of tumor cells for analysis. In contrast, most interviewees expect liquid biopsies to be conducted in addition to solid tumor testing when a biopsy is available. As a result, sequencing of cell free DNA found in blood using NGS platforms will likely be used in conjunction with solid tumor biopsies for diagnosis, therapy selection, and subsequently used as the sole disease monitoring tool. For the most part, experts are optimistic that with enough supporting data from sufficiently rigorous clinical studies, liquid biopsies usage will supplement, or even possibly surpass, that of its more invasive counterpart in the future.NGS will be necessary in informing immuno-therapy treatment. Another area within oncology in which NGS is expected to play a role is cancer immunotherapy (CIT). CIT drugs stimulate the patient’s immune system to recognize neo-antigens (cancer specific proteins), and subsequently attack cancer cells. At first glance, it may seem that the paradigm shift of viewing cancer as a disease of the genome to viewing cancer disease of cells will decrease the need for NGS. However, recent studies suggest that determining the tumor mutational load and type of mutation may be an important predictor of CIT drug effectiveness—the more mutated and phenotypically different cancer cells are to healthy cells, the more likely they are to be recognized by immune cells during therapy.Illumina platforms remains dominant in the clinical NGS market. We expect that the majority of clinical NGS tests will be performed on Illumina platforms, specifically the HiSeq, given the high familiarity, adoption, and customer satisfaction with these platforms. However, we also expect PacBio’s Single molecule real time (SMRT) technology with its long read capability to gain traction, especially among users interested in investigating structural variations, microbial genomes, or the ~15% of the genomes that is “dark” to short read sequencing technologies. One notable breakthrough using long read sequencing technology is within human leukocyte antigen (HLA) typing. HLA genes encode cell surface proteins that allow the body’s immune system to distinguish self from foreign cells, and are extremely diverse and polymorphic across the population. In practical applications, HLA typing is especially crucial in determining donor-recipient match in organ transplants to minimize risks of rejection. Previously, available technologies could only sequence each HLA gene of interest in fragments, often resulting in errors and ambiguity in alignment of these fragments, and requiring multiple methods to be used in conjunction for validation of results. However, in a recent paper on HLA typing using NGS, Mayor et. al were able to utilize PacBio’s long read technology to address these problems. In their paper, they announced that through the sequencing of merely 7 samples, they were able to identify 8 novel HLA Class I sequences, 4 of which were novel alleles.Overall, it seems that NGS has the potential to transform our understanding of health and disease, and we are excited to continue tracking this rapidly developing field.To learn more about the NGS market, including detailed information on market size, segmentation, growth and trends, see DeciBio’s 2015 NGS Report.Disclaimer: Companies listed above may be DeciBio clients and/or customers.---

Author: Susan Zhou, Analyst at DeciBio Consulting, LLCConnect with Susan Zhou on Linkedinwww.linkedin.com/in/susan-zhou