Authored by Gaëtan Fraikin, CEO, Addictive Health
This is part three of a timely 4-part series covering key aspects of precision medicine for anyone interested in understanding (1) what it truly is, (2) how genomics powers it, (3) what genomics will expand to and what other data modalities will eventually be added to the mix, and (4) what disease areas will benefit from it.
Part 1 - Defining precision medicine and looking at its future
Part 2 - Leveraging genomics as foundation
Part 3 - Going beyond DNA and genomics
Part 4 - Going beyond cancer
Beyond DNA, beyond tissue and beyond cancer
DNA is the foundation of precision medicine. Cancer is the focus. Cancer is where most funding, research and solutions go to today. But even with such a level of focus, we still have a long ways to go. According to Cindy Perettie, CEO at Foundation Medicine (Genennews, November 2019), as many as 60% of advanced cancer patients are currently not receiving any form of genomic testing. And testing is just one stepping stone towards true precision medicine. There’s more advances needed in genomics beyond DNA for a multi-dimensional understanding of cancer and other diseases, blood is becoming a fast growing sample for early detection, disease progression and monitoring, and cancer is not the only disease that can benefit from precision medicine. Let’s have a closer look.
Multi-omics and multi-modality
Let’s review the various “Omics” as well as other key modalities, what they are and what they bring to a multi-dimensional picture for precision medicine.
DNA (Genomics)
The obvious. Unprecedented advances in genomics are now enabling the acceleration of precision medicine, by completely redefining healthcare. Quick look back: In the 1980s, the polymerase chain reaction (PCR) was a revolution enabling the understanding of the genome at the gene level. In the 1990s’, the advent of the microarray enabling large-scale genotyping and gene expression profiling studies was the next step forward. In 2003 the first human genome was decoded at an enormous cost of $3 billion, And today, a whole genome sequencing (WGS) can be performed for less than $1,000 through High-Throughput Next Generation Sequencing (NGS), with the next target cost per genome set at $100 by the industry leader in NGS instruments, San Diego based sequencing instrument uncontested leader, Illumina.
RNA (Transcriptomics)
Although the amount of knowledge we can extract from DNA analysis is significant, DNA is found to be not sufficient to have a complete understanding of health and disease. A growing number of publications are showing the variability between DNA mutations and RNA and/or proteins expression. In simple terms, two individual with the exact same DNA sequence may have different downstream events (RNA, Protein). Therefore, RNA is now seen as a potentially more biologically relevant data source. Today’s NGS-based RNA sequencing enable the measurement of the entire transcriptome and non-coding RNA, and RNA in situ hybridization (RNA-ISH) - single-cell analysis from RNA. But is it still a highly complex thing to achieve.
These two data types are the most common and foundation for most clinical precision medicine advances today. But other areas are being researched actively and will possibly be added as modalities in the near future.
Proteins (Proteomics)
The entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. In cancer, the differences in protein expression can help identify novel cancer signaling mechanisms.
Epigenomics
A record of the chemical changes to the DNA either via reproduction or environmental conditions. This is currently an active topic in cancer research as tumors undergo a major disruption of DNA methylation.
Microbiomics
We’re referring to the gut microbiome, defined as the totality of microorganisms, bacteria, viruses, protozoa, and fungi, and their collective genetic material present in the gastrointestinal tract (Source: Joshua Lederberg). The gut microbiome plays an important role in health by helping control digestion and benefiting the immune system and other aspects of health. An imbalance of unhealthy and healthy microbes in the intestines may contribute to weight gain, high blood sugar, high cholesterol and other disorders (Source: Healthline).
Metabolomics
The complete set of small-molecule chemicals found within a biological sample. The metabolome reflects the interaction between an organism's genome and its environment. As a result, an organism's metabolome can serve as an excellent probe of its phenotype (i.e. the product of its genotype and its environment). Almost every factor affecting health – from genetics and the microbiome to disease and lifestyle – exerts its influence by altering metabolite levels.
There’s a long way to go to fully leverage genomics in all its dimensions. And you guessed it, beyond genomics, other critical modalities are going to play a vital role too.
Medical imaging
Also and historically called “Radiology". It includes a variety of modalities such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, positron emission tomography (PET) and ultrasound. It has been lately challenged by blood-based circulating tumor DNA (ctDNA) to become much more precise and detailed.
Tissue pathology
Applied mostly to cancer, with significant advances lately in image analysis and decision support for pathologist leveraging AI and machine learning.
Phenotypic and health data
Includes disease symptoms, relevant demographic data, physical traits and health history. Most of that data is locked in electronic health records (EHR) today.
Imagine a future where every individual’s health is managed through multi-level genomic data, alongside other key modalities, to prevent diseases or maintain health, detect disease early, and treat disease and condition in a targeted and predictable way. We have a long way to go but we are on the right path.
Continue to Part 4 to learn about liquid biopsy, cancer and the other disease areas that are next on the precision medicine target
By Gaëtan Fraikin / CEO / Addictive Health / www.addictive.health / + 1 760 580 3908 / gaetan@addictive.health