Interview with Jay Shafto: Stay focused on one goal - Providing human genome sequencing at a low cost

Jay Shafto, the Principal Process Engineer of Complete Genomics, joined CG at the very beginning with Dr. Rade Drmanac. He has been working with Rade since his first startup.

Q: Can you tell us more about yourself and what’s your work at Complete Genomics?

A: At CG, I worked on substrate and load process development in the early years, and then on data monitoring and troubleshooting when we were sequencing as a service. Now, I’m back to load and substrate chemistry for higher density and longer read-length applications in R&D. My team of three, including myself, is working to push sequencing cost per base down by increasing read length and DNB density. We’re exploring new ways to increase DNB size and array density simultaneously.

Q: Can you describe a typical day or daily routine at work? Can you help us understand the major responsibilities of a Principal Process Engineer?

A: Most of my time is spent in the lab, in meetings, writing emails, or analysing data, much like other R&D professionals. My team operates within the larger Biochemistry/Bioinformatics group under Rade, specialising in DNB array loading R&D. I have regular meetings with them, engineers, the library R&D group, the sequencing chemistry group, and outside vendors. I help everyone understand the core DNBSEQ™ technology as we explore new paths. This involves explaining what works and what doesn’t, what we know and what we don’t yet know, and how we can adapt the technology to new applications. A lot of my work revolves around interpreting data and problem-solving.

Q: What are the common challenges you face in daily work, and what are the most valuable lessons you’ve learned?

A: The biggest challenge has been building a better theory of how our array loading process behaves, allowing us to troubleshoot problems quickly. Every researcher has a working model, and we often make new discoveries empirically. A good theory saves time and money. Another challenge is identifying hidden trends in huge, multi-format datasets across independent experiments. It’s harder without access to customer data. I’ve learned that unintended consequences from upstream process changes can be costly. Bubbles are bad. Always aliquot critical reagents, include experiment controls, and label axes on graphs!

Q: Any advice for younger scientists interested in becoming a Principal Process Engineer?

A: Keep learning every day, stay excited and open-minded. Make yourself available to help. Work independently and collaboratively. Be able to lead and follow. Learn both lab work and programming. Divide and conquer to isolate problems. Be patient but seize opportunities.

Q: You worked with our CSO Rade at his first startup Hyseq and then joined CG. What attracted you most to work with Rade for so long? Is the platform or team leader more important to you?

A: From the start, it was a good fit. The team Rade built at Hyseq was amazing, the work challenging, and I was able to contribute while learning. Rade and Snezana have influenced more than half my life. Long-term work relationships like this are rare and valuable. Rade is a great technologist and fosters a collaborative style, engaging everyone, inviting challenges, and encouraging scientific creativity. There’s also humility, optimism, intelligence, and drive, all steering in the right direction.

Q: Principal Engineers mentor others with ambition to help their growth. Tell us about your team, how many members, and what teamwork impressed you most lately?

A: Dr Ting Wang joined in May 2019 and has been a great contributor for four years, improving HD load, post-load, and large DNB in-situ growth. She has a background in chemistry and computer science. Dr Khan Islammudin joined in October 2021 and has been working on load, bringing microbiology and enzymology expertise. The three of us meet twice a week, recently focusing on high copy number DNB methods. I value working with both and believe they will continue CG’s tradition of creative risk-taking. Both have recently improved large DNB array quality.

Q: How do you feel about Complete Genomics’ culture and values?

A: CG evolved from a high-tech engineering group fused with Callida’s biotechnology team, supported by a Silicon Valley venture capital model – aiming high is essential. The cultural values encouraging good research come from experienced leadership: mutual respect, humility, open-mindedness, skepticism, sharing credit, listening, valuing creativity, and excitement for discovery. With Rade’s goal-oriented direction and this culture, we consistently achieve what others might consider impossible.

Q: You’ve witnessed major CG milestones, like inventing CoolMPS* and stLFR*, and commercial sequencer launches. Which moment impressed or made you most proud?

A: There are many. For me, key moments include loading patterned arrays for the first time, the first automated DNB sequencers, fast TDI imaging on Blackbird, critical quality improvements on BBD, and in-situ DNB growth reducing split rates. The DNBSEQ-G400RS* and DNBSEQ-T7RS* instruments are impressive. Sequencing and assembling our first genome in 2009 was a milestone. In early 2007, achieving the first high-occupancy patterned load just before my son’s birth was pivotal. Now, my son is 16 and CG is turning 18. I’m proud to see DNBSEQ technology go global.

Q: What do you think are the most significant advances CG’s technologies can bring to biological research and to people’s lives?

A: DNA sequencing is foundational to modern biology and biotech. The analogy often used is the invention of the microscope, which led to Robert Hooke’s first publication on cell structure. We’re building DNA microscopes. I anticipate applications in directed evolution, artificial life, studying mosaicism in cancer, and other areas. I hope these advances benefit all.