Data-Driven Precision Medicine Part Two | Leveraging Genomics as the foundation.

Updated: Feb 24, 2021

Authored by Gaëtan Fraikin, CEO, Addictive Health

This is part two 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

Genomics is the foundation

Genomics is at the core of what’s been propelling precision medicine forward. The genomic technological revolutions (described below) enabled dramatic cost reduction of sequencing, with accelerated discovery and the birth of clinical genomics beyond research. But this simple term contains a tremendous amount of complexity in technology, workflow, and components in a complex ecosystem. The good news is that we already have today all the necessary components for true sample-to-answer clinical genomic solutions. But in most cases, labs, biopharma companies and medical devices companies are left with the highly complex task of engineering a solution themselves, to fit their specific needs. A great example: San Diego (My home town) based Rady Children’s Institute for Genomic Medicine led by the renowned Dr. Stephen Kingsmore. In a paper titled “Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation", the team outlines the work that went into engineering that solution and the results it generated. Needless to say that few labs around the world would be able to match what Dr. Kingsmore and his team accomplished. Let’s break down the various components needed to deliver a true end-to-end clinical genomics solution, from sample to answer - the necessary foundation for precision medicine.

Sample collection

Everything starts with biological material from a patient. To get DNA, there are 3 main sources: saliva, blood and tissue. The sample type depends on the testing type to be performed.

Sample preparation

To go from a human sample to an analysis ready sample, it must be prepared. Next-generation sequencing (NGS) library preparation involves generating a collection of DNA fragments ready for sequencing. Leading brands in the space of sample preparation include Roche, Agilent, Thermo Fisher, Illumina, Becton Dickson, 10X Genomics, Fluidigm and Lexogen.

Sequencing instruments

Once the sample is prepared, it needs to be run on a sequencer for primary analysis: Process of determining the order of nucleotides (ACGTs: adenine, cytosine, guanine, and thymine) in DNA. Leading brands in the space are Illumina, BGI, Thermo Fisher, Pacific Bioscience and small challengers with new technologies. On the technology side, the leading one is Sequencing by Synthesis (SBS - pioneered by Solexa acquired by Illumina). Other technologies include Nanopore Sequencing, from Roche (Stratos Genomics), Nanopore, and Quantapore, Sequencing by Binding (SBB - Omniome), Single Molecule Real-Time (SMRT) Sequencing (Pacific Biosciences) and others.

Diagnostic assays

Assays cover a range of disease areas including cancer, reproductive health, micro-organisms, infectious diseases, neurology and rare diseases. Most assays are “targeted” - focused on specific genes. On the other side of the spectrum, for rare diseases or undiagnosed conditions, there's Whole Exome Sequencing (WES) - sequencing of the exome, the 1% protein coding regions of the genome and Whole Genome Sequencing (WGS) - the entire genome. Tests are sold in two distribution channels today: Direct to consumer (DTC) with 23andMe, AncestryDNA, Vitagene, Veritas, Phosphorus, and through physicians, including Guardant Health, GRAIL, Invitae, Color, Freenome, Exact Science and Veracyte in oncology, Roche (Harmony), Natera, Illumina and Sequenom in reproductive health (NIPT), ArcherDx (Acquired by Invitae), Adaptive, Amber Genetics and Myriad in broad range of disease areas portfolio), Cepheid, Luminex and Karius in infectious diseases and Centogene, Blueprint Genetics in rare diseases.

Variants analysis software and decision tools

Once the A,C,G and Ts within the sample are identified, software - called bioinformatics software - is needed to identify variants from a genome of reference. Those applications enable the analysis of multiple biomarker types — fusions, insertion/deletions (indels), single nucleotide variants (SNVs), and copy number variations(CVNs). That's the secondary analysis. Beyond that, tertiary analysis is called "interpretation". Interpretation involves the biological classification of identified variants, determination of the clinical relevance of these variants, their action-ability in terms of treatment options, and is ultimately provided to the treating physician in the form of a "report". Leading brands include Seven Bridges, DNANexus, Illumina, Congenica, Fabric Genomics, PierianDx, Syapse, Emedgene and Sophia Genetics.

Genomic Data Management Solutions

The exponential amount of data being generated must be compressed, stored, secured, managed, shared and compliant. According to, Genomics is now considered a legitimate big data field – just one whole human genome sequence produces approximately 200 gigabytes of raw data. If we manage to sequence 100M genomes by 2025 – we will have accumulated over 20B gigabytes of raw data. The massive amount of data can partially be managed through data compression technologies, but that doesn’t solve the whole problem. What’s more, sequencing is futile unless each genome is thoroughly analyzed to achieve meaningful scientific insights. Genomics data analysis normally generates an additional 100 gigabytes of data per genome for downstream analysis. So this could be the biggest bottleneck in the space. Brands in this space include Lifebit Biotech, Bluebee (Now Illumina), Petagene and Genomsys.

Drug discovery

This is about providing a combination of all components described above to help pharmaceutical companies accelerate drug discovery and development, economically and reliably. Brands in this space include Genomic Medicine, Genome Medical, Deep Genomics, Cofactor, Genomics PLC and highly innovative and disruptive Tempus.

Precision medicine Integrated enablers

This is the integration of sequencing, analysis, treatment options, clinical trial options and drug discovery, ideally driven by artificial intelligence and machine learning. Organizations in that model are the one closest to accelerating data-driven precision medicine by leveraging all upstream components and adding real world data, artificial intelligence and machine learning. Key brands are Foundation Medicine (Roche), Tempus, Genuity Science (Formerly WuXi NextCODE) and MedGenome.

Synthetic biology

A new field. According to Nature, Synthetic Biology is the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems for useful purposes. Examples include new kinds of therapeutics, diagnostic products, forms of targeted deliveries, pharmaceutical products and vaccines. Key brands in this space include Twist Biosciences, Microsoft Research Station B, Atomwise, Arzeda, Distributed Bio, Precision Bioscience and Beam Therapeutics.

/ Continue to Part 3 to learn about the need to go beyond DNA and beyond genomics to deliver on the full promise of precision medicine

By Gaëtan Fraikin / CEO / Addictive Health / / + 1 760 580 3908 /

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