Recent Developments in Genomic Sequencing

Over the past two decades, the sequencing landscape has undergone a transformation, with new technology catering to a variety of needs. This evolution has been driven by innovation and competition, resulting in a significant decrease in the cost of sequencing, enabling larger-scale projects.

One area where cost reduction has been particularly important is RNA-seq, where low cost and high yield might be more crucial than the highest accuracy. This has opened up opportunities for sequencing a larger number of samples, thereby increasing the scope of research.

As the cost of sequencing continues to decrease, sequencing cores may face challenges due to decreased revenue per sample. They need to process more samples to recoup costs, but this increased throughput could also become a differentiator in the market.

Speed could become a bigger differentiator, especially for clinical applications. For instance, PacBio's SPRQ chemistry has increased yield and lowered the required input, allowing samples that couldn't previously be used to now be sequenced more quickly.

In the context of finding low-frequency mutations, accuracy is crucial to read through background noise. However, there is still a big cost differential for long reads, but as more competition appears, this could change.

Long-read sequencing platforms are evolving, but the cost of data storage remains a significant consideration due to its expense. This is particularly relevant as the amount of data generated by these platforms continues to grow.

Niall, from a renowned institution, predominantly uses PacBio technology and finds long reads interesting because they unlock new insights and provide a higher resolution, aiding in functional discovery. Niall's institution has been piloting rare disease diagnostics in collaboration with Boston Children's Hospital, using long-reads to increase the diagnostic yield.

Claire's organization uses the PacBio platform for de novo genome assembly of non-traditional model organisms. However, some field samples can be degraded and will preferentially be sequenced using Oxford Nanopore technology, which is effective for sequencing degraded samples and is also good for direct RNA sequencing and detection of RNA modifications.

Bony suggested the need for new standards for tissue collections and storage, implementing new policy framework and carrying out baseline studies, and moving beyond formalin to find good alternatives for smart storage preservatives that can preserve tissue integrity as well as nucleic acids.

Recent announcements by companies like Ultima and Roche have hinted at new sequencing platforms, further fueling the advancements in this field. Current advances in sequencing include the rapid growth of next-generation sequencing (NGS) technologies offering ultra-high throughput, scalability, and speed. Key players like Illumina and Thermo Fisher have introduced innovative NGS-based products, supported by government research grants due to their superior cost-efficiency compared to other diagnostic methods.

Furthermore, new AI systems inspired by brain mechanisms, such as China's SpikingBrain-1.0, greatly accelerate DNA sequence analysis with much lower data requirements, enhancing sequencing efficiency. Illumina's Protein Prep uses NGS-based proteomics to analyze thousands of protein targets simultaneously, improving biological understanding and drug discovery. Advances in related fields like precise gene editing with CRISPR/Cas9 also contribute to progress in genomic research.

Despite these advancements, the cost of a genome sequence is not the main barrier to adoption in the clinic; logistics and reimbursement play a larger role. Nevertheless, the future of genomics looks promising, with continuous advancements in technology and methodologies.