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10x Genomics: Culture of Collaboration And A New Product Engine



By Allison Proffitt

June 4, 2020 | At 10x Genomics, culture is key says Ben Hindson, co-founder and CSO. In early March, when we could still sit together in the company’s sunny California offices, Hindson outlined a winning recipe bringing together software folks, hardware experts, biologists, chemists, and data scientists. In fact, the 10x Genomics company co-founders represent similar diversity: Hindson is a chemist by training. Serge Saxonov, CEO, is a bioinformatician who previously served as the founding architect and director of R&D at 23andMe. Kevin Ness, now CEO of Inscripta, but formerly COO and CTO at 10x Genomics, has an engineering background.

Hindson knows better than to claim that the 10x formula is unique; lots of life sciences companies these days aim to bring together diverse teams. The difference, he argues, is that at 10x it works.

“A lot of places have it, but they don’t actually work together. They don’t really like each other,” he observed. “We’ve created this culture where we kind of rely on each other.”

So how does a company make a varied team really like each other and work well together? “First you have to give them a really hard problem,” Hindson said. “They get their heads together and they start generating results.”

There’s no shortage of really hard problems these days.

In early March when I toured the offices—new space in Pleasanton, California, bought before the company’s September IPO—Hindson already knew of at least one SARS-CoV-19 paper using the 10x platform, testing samples from a patient in a Shenzhen hospital. Since then, the platform has been used in SARS-CoV-19 research published in Nature, Nature Medicine, Cell, EMBO Journal, Science Immunology and more. More papers are in the pipeline and available on bioRxiv and medRxiv.

10x Genomics’ vision is to “master biology”, Shernaz Daver told me in March. Daver is an advisor to the company, and an executive advisor with Google Ventures. She joined Hindson for my visit, enthusiastically sharing the company’s growth and future plans.

“We have been working on COVID-19 and supplying our products to academic labs, research institutes and pharma companies around the world.  We are at over 50 places that are using 10x products to fight this deadly disease,” Daver said in an email update last month. She mentions therapeutics and vaccine work at Vanderbilt University, Shenzhen labs in China, Imagine Institute in France, and Merck among others.

But the company’s plans extend beyond the current pandemic, of course. 10x’s recent growth includes nearly doubling its workforce in the past year and acquiring Epinomics and its ATAC Seq technology in September 2018 and Spatial Transcriptomics, now its Visium spatial genomics technology, in December 2018. The company has 700 patents or patent applications, a research center in Sweden (thanks to the Spatial Transcriptomics acquisition), a sales office in Singapore, and plans to open a manufacturing facility in Singapore later this year.

Expanding the Product Suite

The business is now divided into two “families” Hindson said: the Chromium single-cell sequencing technology and the Visium spatial genomics technology that came from the Spatial Transcriptomics acquisition.

Chromium is the company’s oldest existing product. In January at the JP Morgan Healthcare Conference, the company quoted an install base of the Chromium Controller single-cell sequencer for more than 1,600 instruments. Hindson sees a broad market with much growth ahead of it. “We’re nowhere near the limits of that technology,” he said.

“Tens of thousands of labs out there that could have their own Chromium Controller on their bench and run a suite of our assays, Hindson said. “We’re seeing the amount of reagents that people use; it’s very healthy. Even as we get downstream [of the purchase], we see that usage continue in terms of how much instrument/reagent they’re using. The people who have had it the longest are also increasing the usage, which is also nice.”

10x Genomics has combined the Chromium single-cell gene expression capabilities with the ATAC Seq technology, announcing Chromium Single Cell ATAC + Gene Expression at AGBT in February.

The tool lets customers measure both epigenetic and gene expression markers from the same single cell at scale simultaneously. “The performance is equivalent to running each one individually, but you can see things that you wouldn’t necessarily see if you ran them separately and combined them computationally,” Hindson said.

Customers’ requested increase in volume and efficiency are driving the 10x business, Hindson said: doing more, faster, cheaper. Already routinely doing 1,000, 10,000, and 100,000-cell experiments, the 10x user community is asking the company for even more scale, Hindson said. “What people want to get to next is routine million-cell experiments and 10 million… It’s kind of like the next wave,” he predicts.

Combinatorial drug screens, immunology, and expression quantitative trait loci (eQTLs) are all driving the need for gene expression on a large scale. “That really comes down to not just the bulk gene expression, but which expression is going on in which cells,” Hindson explained. “When you look at the individual cell level, you may get the total opposite answer of which variants were responsible for disease states.”

CellPlex, also announced at AGBT, is meant to improve scale. Customers can run experiments on a scale of up to 160K cells or multiplex up to 96 samples per run on an 8-channel chip. In combination with other 10x Genomics innovations, CellPlex will enable routine million-cell experiments.

And last month the company launched its Targeted Gene Expression Solution. When used in conjunction with 10x Genomics Single Cell Gene Expression workflows, the Targeted Gene Expression Solution provides expression profiles of a set of targeted genes, from hundreds to thousands of single cells in suspension.

“It can also increase your sensitivity for low-expression genes somewhat, but importantly it can reduce the cost of your experiment by reducing the amount of sequencing you have to do—that’s significant—which enables you to then run more samples,” Hindson explained.

The tool launched with three pre-designed gene panels—a Human Pan-Cancer Panel, Human Immunology Panel, and Human Gene Signature Panel—with validated probes for more than 1,000 genes per panel. A Human Neuroscience Panel is coming soon, the company says, as well as custom panels with customers’ own gene lists. The tool is currently for single cell research, but 10x expects to release optimized protocol, support, and software for targeted panels with spatial gene expression in September 2020.

On the spatial genomics side, early adoption of the Visium product is really promising, he said. “Spatial Transcriptomics had some great tech, some really early assets, and some great people. Then we applied the 10x way of doing things and some of the assets we developed and kind of took it to the next level.” 10x increased the resolution of the arrays, picked up 300% more genes from each region, and refined the workflow decreasing run time from three days to eight hours.

Visium is bringing new customers, Daver said, particularly within pharma and for brain applications. 10x hopes to create a network of Visium users. “There seems to be a lot of interest and excitement over spatial,” she said.

Future Vision

Hindson feels a strong commitment to the 10x user community and rolls out new products to key beta tester sites—academia, pharma, biotechs, and government labs—for feedback and insight into future applications. Through that network, “we get to test samples that we don’t have access to, to see whether there are things we may be missing, or what the insights may be,” he said.

10x tries to announce new products early and often, Hindson said. A 10x goal, Daver pointed out, is to be an innovation engine—to constantly bring new products and test how they succeed in the market.

“Our customers want to be able to plan,” Hindson said. “If they know something is coming from us, they may not spend the energy developing it themselves. They appreciate that because they can go spend their time on something else.”

Biotechs, in particular, have been using the 10x platforms and products as core discovery engines more and more in the past 5 years, Daver noted. The 10x offerings help these biotechs get more products to market more efficiently. “The idea,” she said, “is can you create an ecosystem of these different companies and research labs that couldn’t do things as efficiently if 10x was not there. We’re seeing a lot of that right now.”

The company plans to launch the 10x Genomics Cloud this year, tying all of the product offerings together—first for US customers, then globally. “It’s going to enable even more downstream folks to not have to worry about buying a bunch of these blade servers, which I’ve done here at 10x,” Hindson laughed. “You can just use the cloud.” Existing customers will be able to access a standard set of analysis at no cost, and in the midst of a pandemic, that seems like a very timely offering indeed.

“There’s more opportunity for collaborative opportunities. A lot of people want to compare datasets across different countries, et cetera,” Hindson said.

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