Biotech
Multiomics Are The Next Step In Biotechnology
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The Genomic Revolution
Most of the progress in medicine and even agriculture in the last two decades has been on the back of the genomic revolution. By knowing the genetic makeup of living organisms, scientists can find new targets for therapies, new ways to optimize the production of valuable materials, and even start to change the genome itself, thanks to gene editing. This is now becoming a big business, with the first gene editing therapy approved (Casgevy) coming with a price tag of $2.2M.
What drove this revolution is the much deeper understanding of biological processes thanks to genome sequencing. Still, the genome is a rather crude dataset. It is a little like a full dictionary, with the exact “orthography” of each protein in a cell. But a living cell is more like a complete novel, in which how the “words” (the RNA and proteins) are arranged is much more relevant.
From Genomics To Multiomics
The complexity of even a single cell, and even more a full human body, is why more advanced analytical methods than genomics are needed. And there are many:
- Transcriptomics: the analysis of mRNA.
- Proteomics: the analysis of proteins, including the modification of proteins with sugars (“post-translational”).
- Metabolomics: the analysis of chemical compounds and the metabolism.
- Epigenomics: the modification of the genome without affecting the genetic sequence, or “epigenetics”.
- Microbiomics: the analysis of all the microbes living inside or on the body.
- Single-cell multiomics: the multiomics analysis on individual cells.
- Spatial biology: analyzing in 3D the location of specific mRNA, proteins, or cells.
These analytical methods are often orders of magnitude more complex than “simple” genomics. Each can and ideally should be combined with the other to give a better picture of the real complexity of a living organism.
When combined, they allow for “multiomics” analyses.
A Multiomics Data Explosion
Proteomics
The capacity for protein analysis has increased by several orders of magnitude in the span of only a decade.
As shown in this graph from ARK Invest (with a logarithmic scale), hundreds of thousands of proteins can now be analyzed in one hour, with proteomic methods able to distinguish up to 10,000 proteins per sample. The cost per sample has also fallen steadily, from $1,000 in 2011 to just $100 in 2023, or a decline of 23% annually.
Source: ARK Invest
This has radically accelerated the discoveries of cancer biomarkers and the development of precision therapies, a topic we investigated in-depth in “Treating the Untreatable with Precision Therapies – A $4 trillion Opportunity?”.
Transcriptomics
mRNAs is the “instruction manual” to the genome “dictionary.” The form and quantity of mRNA are really what dictates how the gene is expressed and used in the cell.
The problem with early transcriptomics was that it had to analyze at least thousands of cells at once, if not millions. This erases all the details of changes in mRNA that were transient in time or too localized.
This has changed with the possibility of single-cell RNA analysis, revolutionizing our understanding of cancer. With this, we can understand exactly which gene is responsible for cancer and which sub-type of cell is actually doing it.
Source: ARK Invest
Other -Omics
While more recent, the other analytical methods are no less promising.
Spatial biology allows the analysis of single cells and how different cells and RNA or proteins interact with each other. In real-time if needed. This opens entirely new fields of scientific research, something we discussed further in our article “Spatial Biology: Nanostring vs. 10x Genomics”.
Microbiomics makes it possible to use the bacteria in our gut or on our skin for new therapeutic methods. For example, autism spectrum disorder has recently been linked to the gut microbiome. Which correlates with “studies demonstrating long-term benefits on autism symptoms and gut microbiota through microbiota transfer therapy”.
Epigenomics could become the next step of precision therapies, with the possibility of fine-tuning the gene expression of cancer cells, for example.
Source: National Library of Medicine
“Epigenetic rejuvenation” is also a possibility for reversing aging, one of the methods discussed in our article “Aging is a Part of Life – That Doesn’t Mean We Can’t Put Up a Fight”.
AIs To Help Process Multiomics Data
The result of the decreasing costs and increasing capacity for multiomics analysis is a flood of data like never before. It is quickly becoming beyond any researcher's capacity to sift through these data to find relevant points manually.
Luckily, the multiomics revolution is occurring while AI becomes increasingly more capable.
AI, machine learning (AI/ML), and automation are already powering drug discovery. This in itself should help reduce significantly the cost of drug discovery, thanks to AI screening library of existing and potential drugs, and predicting the probable outcome “in-silico”. This alone could grow the precision therapy space by a 26% CAGR rate during the next seven years,
from ~$820 billion in 2023 to ~$4.5 trillion in 2030.
Source: ARK Invest
But drug discovery is just the first step. AI can also be used to predict the chemical properties of new molecules or proteins, like the AI tool “Distributional Graphormer” from Microsoft.
Source: Microsoft
AI can also predict if a molecule will be toxic without having to test it on living cells or animals. It can be mixed with automation to run at-scale experiments, including “Organ-on-a-chip” simulations or automated experiments (automated liquid handling, “invivomics”, or microsynthesis)
Lastly, AIs and IT integration could improve clinical trial designs, with more adaptative trials, more biomarkers tracked, or even decentralized trials.
Source: ARK Invest
Multiomics Stocks
1. Pacific Bioscience (PacBio)
Started a few years after genome sequencing industry leader Illumina, PacBio has been the smaller player in genome sequencing since. Despite its smaller size, the company's equipment has stayed on the top level of performance.
It is also the 8th largest holding of the ARK Genomic Revolution ETF.
PacBio recently acquired Omniome in 2021, giving it an advantage in accuracy for reading very long or short genetic sequences. This advantage was reinforced with the later acquisition of Apton for $110M in August 2023, which also specialized in short read, high throughput (SR-HI).
Source: PacBio
PacBio's Onso systems are now starting to ship to customers, and its launch has been described by the company as the “best start in PacBio history”. It will specialize in short sequences, while its Revio HiFi System will be able to read long sequences and work 24/7, making it read 1,300 full human genomes per year (roughly 4/day). Later, the Revio HiFi will be replaced by the HT SBB system, which will likely integrate Apton technology.
Pacbio expects long sequences to grow much quicker than the broader NGS (Next-Generation Sequencing) market and claims its systems are 10x more accurate than the competition.
Source: PacBio
Interestingly, it could also bring down the total cost of genome sequencing. Without getting too technical, short sequences need to be reassembled in a comprehensive whole. So a $500 short read genome can quickly need extra analyses costing a total of $1,500 to be actually useful as a diagnostic tool.
So a $950 Revio long sequence analysis avoids this step and comes out cheaper for diagnostic application.
PacBio's focus on high-precision/long-sequence analysis should give it an edge in diagnostics for the next few years. PacBio management believes this could boost the company's market penetration in human genomics from the current 5% to 10% and in oncology (cancer) from 1% to 5%.
While PacBio is mostly focused on its decades-old competition with Illumina, it might also have to contend with Oxford Nanopore in the diagnostic/long-sequence market.
2. 10x Genomics Technology
10x Genomics is a leader in spatial biology, which studies the genome and transcriptome in 3D, allowing visualization of the activity of genes at the cellular or even intracellular level.
The company was founded in 2012, with Serge Saxonov among its founders, the director of R&D of the personalized genome testing company 23andMe.
It is also the 12th largest holding of the ARK Genomic Revolution ETF.
10x Genomic grew using a mix of R&D ($1B+ investing in R&D so far) and acquisitions to branch out in many different -omics fields. Notably, its Visium platform for tissue spatial transcriptomics was obtained by acquiring Spatial Transcriptomics in 2018.
This is also how 10x Genomics would acquire its Xenium platform for single-cell visualization by acquiring Readcoor and Cartana in 2020.
In 2020, it would also launch the Chromium platform, updated the year after to Chromium X, for single-cell RNA sequencing.
Through the acquisition of Tetramer Shop in 2021, 10x Genomics would also launch BEAM (Barcode Enabled Antigen Mapping) in 2022. It allows researchers to identify components of the immune system in detail. This could be very impactful in research on immunity and new diseases.
10x Genomics acquisitions timeline- Source: 10x Genomics
The company also earned in September 2023 a critical victory against its main rival, Nanostring. Nanostring is for now banned from selling its CosMx Spatial Molecular Imager (SMI) instruments in most of the EU for infringing on 10x Genomic patents.
This led to the announcement that Nanostring is filing for bankruptcy and exploring potential sales in February 2024.
NanoString accused 10x Genomics of levying its lawsuits “with the apparent goal of shrinking the competitive landscape for different spatial biology platforms to the detriment of the public good”
Overall, 10x genomics seems to be in a position to establish a solid lead in the spatial biology market, including single-cell transcriptomics and antigen mapping.
The company is still in its early stages, somewhat similar to the early days of Illumina and Pacific Biosciences. For now, spatial biology is confined to the world of academic and fundamental research. But like many biotechnologies, it might one day become widespread, slowly become a medical tool, and then become a “routine” test. In any case, the growing pool of installed machines should drive sales of consumables and revenue growth.
