PGDx machine learning approach outperforms existing mutation detection methods in study

September 5, 2018, Personal Genome Diagnostics
Credit: CC0 Public Domain

Personal Genome Diagnostics today announced that its machine learning-based technology, CerebroTM, outperforms existing methods to identify tumor-specific or somatic mutations, enabling more accurate NGS clinical test results. The study, published in Science Translational Medicine, was conducted using analysis of data from 1,368 samples.

"Increasingly, NGS diagnostic tests are being used to identify genetic alterations that help oncologists make decisions with their patients about the potential effectiveness of therapies. However, different NGS approaches have varying results, calling into question the ability of NGS to detect real ," said Sam Angiuoli, Ph.D., chief information officer at PGDx. "We know it is absolutely critical to get the right answer for patients, so we pioneered the development of automated NGS software that incorporates machine learning strategies to improve the accuracy of somatic mutation detection. As this study reveals, our approach yields better results compared to alternatives and highlights the importance of combining state-of-the-art software and data science in genomic testing."

Cerebro's machine learning approach analyzes a wide variety of characteristics to assess whether any given identified mutation is real. The accuracy of the Cerebro technology was compared to existing methods for somatic mutation identification using simulated and experimentally validated whole-exome and targeted gene analyses of cancer specimens. Cerebro was able to detect tumor alterations with higher sensitivity and positive predictive value (PPV) compared against other methods.

The Cerebro study also evaluated the importance of improved somatic mutation detection in clinical NGS assays. PGDx performed head-to-head comparisons of clinical sequencing with or without the Cerebro machine learning approach, including a comparison of predicted outcomes for patients treated with immune checkpoint blockade.

"Highly accurate mutation detection may be particularly important for biomarkers like tumor mutation burden, or TMB, which correlates with response to immunotherapies. Our data showed improved classification of patients when using Cerebro and highlights the importance of accurate mutation detection on treatment decisions," said Dr. Angiuoli.

This study brings to light the variability in detecting tumor-specific alterations across different NGS tests, underscores the importance of standardization as NGS tests move into more routine clinical use, and demonstrates the higher accuracy of PGDx's solution when compared against commercially available methods from other diagnostic companies.

"Developing a highly-accurate bioinformatics software solution that automates mutation detection is integral to PGDx's approach to create a complete solution, from DNA sample to high-quality patient result," noted John Simmons, Ph.D., Director of Translational Science and Diagnostics at PGDx. "Our decentralized product approach includes optimized assay chemistry combined with a fully automated bioinformatics software platform, which reduces subjective analyses and increases reproducible results. This comprehensive solution will enable local testing in molecular laboratories worldwide, with a faster turnaround of reliable results to support critical clinical decisions."

Explore further: Novel genomics tool enables more accurate identification of rare mutations in cancer cells

More information: D.E. Wood el al., "A machine learning approach for somatic mutation discovery," Science Translational Medicine (2018). … scitranslmed.aar7939

Related Stories

Novel genomics tool enables more accurate identification of rare mutations in cancer cells

March 22, 2018
A new computational method developed by researchers at the New York Genome Center (NYGC) allows scientists to identify rare gene mutations in cancer cells with greater accuracy and sensitivity than currently available approaches.

New ESMO tumor DNA scale helps match patients with cancer to optimal targeted medicines

August 20, 2018
A new scale for tumour DNA mutations which will simplify and standardise choices for targeted cancer treatment has been agreed by leading cancer specialists in Europe and North America. The scale, called ESCAT (ESMO Scale ...

Sensitive new assay finds abnormalities in tumor cells that other techniques may miss

June 18, 2018
RNA-Seq is a new next-generation assay that can detect gene fusions in solid tumor cells with high accuracy and excellent reproducibility. According to a new report in The Journal of Molecular Diagnostics, the assay detected ...

Accurately diagnosing genetic disease prevents cancer, saves lives

March 29, 2018
A single, upfront genomic test is more effective for detecting Lynch syndrome in colorectal cancer (CRC) patients than the traditional multiple, sequential testing approach, according to new clinical data reported by The ...

Broad genetic testing for advanced lung cancer may not improve survival

August 8, 2018
Testing for dozens of genetic mutations in tumors of patients with a common form of advanced lung cancer did not appear to improve survival compared to routine genetic testing, a study led by Yale Cancer Center (YCC) scientists ...

New mutation-testing technology has potential to guide targeted lung and colorectal cancer therapies

June 8, 2016
A new technology suitable for practical clinical testing can detect KRAS gene mutations in lung and colorectal cancers and could thereby facilitate targeted therapies, according to a new report in The Journal of Molecular ...

Recommended for you

Progress in genetic testing of embryos stokes fears of designer babies

November 16, 2018
Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

Gene editing possible for kidney disease

November 16, 2018
For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

DICE: Immune cell atlas goes live

November 15, 2018
Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

Ashkenazi Jewish founder mutation identified for Leigh Syndrome

November 15, 2018
Over 30 years ago, Marsha and Allen Barnett lost their sons to a puzzling childhood disease that relentlessly attacked their nervous systems and sapped their energy. After five-year-old Chuckie died suddenly in 1981, doctors ...

Drug candidate may recover vocal abilities lost to ADNP syndrome

November 15, 2018
Activity-dependent neuroprotective protein syndrome (ADNP syndrome) is a rare genetic condition that causes developmental delays, intellectual disability and autism spectrum disorder symptoms in thousands of children worldwide. ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.