ASeq Newsletter

The ASeq Newsletter explores advancements and challenges within the sequencing technology landscape, focusing on industry dynamics, clinical applications, and market competition. It critically examines the role of major companies like Illumina, emerging technologies, and the impact of sequencing in diagnostics and oncology.

Sequencing Technology Genetics and Diagnostics Market Dynamics Clinical Applications Industry Analysis Technological Innovations Company Profiles

The hottest Substack posts of ASeq Newsletter

And their main takeaways
72 implied HN points 26 Feb 24
  1. The post is a Q&A session with Nava Whiteford, shared on Substack, a platform for paid subscribers.
  2. Nava was asked to participate in a Q&A for a conference, but it's uncertain when or how it will be published.
  3. The post is exclusive for paid subscribers, and interested individuals can subscribe on Substack to access it.
51 implied HN points 05 Mar 24
  1. The post discusses Nanostring creditors identified in bankruptcy proceedings, indicating a Google document with detailed creditor breakdowns and mentions suppliers of 'Compelling presentations for litigation'.
  2. The focus of interest lies in the technical components used in Nanostring instruments, narrowing down the list significantly.
  3. Access to the full post is restricted to paid subscribers.
51 implied HN points 24 Feb 24
  1. 10X Genomics has been involved in several lawsuits related to their patents in the spatial space, with most patents set to expire around April 2031.
  2. There is one patent that expires in 2036, which seems to be focused on imaging systems.
  3. If 10X Genomics continues to enforce their patents effectively, they could maintain dominance in the spatial market for the next 7 years.
51 implied HN points 15 Feb 24
  1. The post discusses experimenting with Atto-532 in a MiSeq for epi-fluorescent microscopy, highlighting the process of preparing and imaging on a microscope slide.
  2. Images taken show varying brightness in different color channels, with Atto-532 matching well with the green LED used in MiSeq technology.
  3. There's an anticipation of potential dye crosstalk, with the expectation of leakage from the G dye into the T channel, suggesting Atto-532 as a good match for the G dye.
36 implied HN points 24 Feb 24
  1. Rumors about layoffs and nepotism at Oxford Nanopore are circulating, potentially impacting the company's share price.
  2. The company's delayed announcement of layoffs raises questions, with some seeing it as a strategic move and others as a demotivational tactic for employees.
  3. The overall strategy of Oxford Nanopore is being called into question, with suggestions that changes may be needed for the company to succeed.
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36 implied HN points 20 Feb 24
  1. In DNA sequencing, methods that ensure one bead and one template per droplet can significantly increase throughput.
  2. Ultima Genomics has been working on a method that allows 100% of beads to have product from a single template, potentially doubling throughput.
  3. Ultima's approach shows promise in reducing polyclonal rates, potentially offering an advantage over existing platforms.
29 implied HN points 02 Mar 24
  1. Protein sequencing using nanopores is a topic of interest, with a recent study highlighting a large state space of 10^25 and using an Oxford Nanopore's R9.4.1 pore with a range of ~10pA.
  2. Investigating patents can provide insights into the current range for DNA sequencing and can spark further contemplation about the future of protein sequencing using nanopores.
  3. The detailed post on protein sequencing and nanopore current ranges is available for paid subscribers, emphasizing the exclusivity of the content.
29 implied HN points 27 Feb 24
  1. The MiSeq flowcell consists of a plastic outer shell with a glass flowcell that clips open and closed.
  2. Measurements indicate a cover glass thickness of around 150um and a 100um channel height on a 1mm substrate.
  3. Unlike other flowcells, the MiSeq uses an all glass construction bonded with optical bonding material and borosilicate glass apertures.
51 implied HN points 09 Jan 24
  1. Illumina has a variety of sequencing instruments in their lineup, which includes different models and variations.
  2. The cost of production for these instruments varies based on the technology and components used.
  3. Rationalizing the Illumina instrument lineup could involve withdrawing some current models and introducing new, more cost-effective options.
36 implied HN points 31 Jan 24
  1. Illumina has a method to potentially double their instruments' throughput, but it may come with a slight decrease in accuracy.
  2. By simultaneously reading both the forward and reverse strands, Illumina can achieve four reads per cluster, doubling the throughput.
  3. Implementing the simultaneous paired-end sequencing approach may be challenging without sacrificing accuracy, but it opens up opportunities for increased throughput in the future.
21 implied HN points 06 Mar 24
  1. The ONT account numbers released today are not directly comparable to previous reports, especially for S1 (MinION) users who appear to have shifted to 'Indirect' sales.
  2. The number of S2 active customers has been revised up to 1210 from the previous estimate of 'around 1100', as stated at JPM.
  3. The count of S3 customers has been reduced to 84 from the previously mentioned '90 large high throughput' at JPM.
36 implied HN points 23 Jan 24
  1. Clinical sequencing market is surpassing research in sequencing.
  2. Oncology is the largest clinical market, with a significant revenue.
  3. Companies like Exact Sciences are prominent players in precision oncology testing.
36 implied HN points 18 Jan 24
  1. Spatial revenue for 10X Genomics is increasing, while single cell revenue growth is slowing down.
  2. There may not be much growth expected in single cell applications for 10X Genomics, but spatial sequencing shows potential for growth.
  3. 10X Genomics faces competition in the single cell market, but may retain a significant market share.
21 implied HN points 21 Feb 24
  1. The acquisition of Solexa by Illumina involved strategic financial decisions and a combination of technology strengths to create a successful sequencing platform.
  2. There were missed opportunities and challenges due to financial constraints and differing viewpoints among key players in the sequencing technology industry.
  3. The early 2000s marked a period of significant innovation and the emergence of next-generation sequencing technologies, with various companies maneuvering to establish themselves in the market.
29 implied HN points 29 Jan 24
  1. Illumina sequencing uses clusters of DNA fragments, which can create issues if not all the fragments are the same.
  2. Unpatterned flowcells may have overlapping clusters leading to ambiguous results.
  3. Patterned flowcells use Exclusion Amplification to prevent cluster overlap and improve sequencing accuracy.
36 implied HN points 06 Jan 24
  1. The NextSeq 550 Imaging System uses 6 identical imaging sub-modules.
  2. Each sub-module has its own camera, focusing electronics, and excitation sources.
  3. The post provides a summary of information based on one of these imaging modules and what's available in patents.
21 implied HN points 17 Feb 24
  1. PPMSeq is a duplex sequencing technique that ensures high accuracy reads by reading both forward and reverse strands of a double-stranded sequence.
  2. Ultima's PPMSeq works by amplifying both strands on the same bead and utilizing a tag to identify their presence, with errors causing radical dephasing which is taken care of by downstream software.
  3. Approaches to implementing PPMSeq on Ultima's platform involve reading both strands in both directions simultaneously or keeping the product on beads in the same orientation, each with its own challenges and considerations.
80 implied HN points 06 Oct 23
  1. The author strongly believes in the power and importance of DNA and RNA sequencing in diagnostics.
  2. Many clinicians tend to delay diagnostic tests unless absolutely necessary, relying on common symptoms and tests first.
  3. Despite the potential of advanced genetic testing, clinicians may be hesitant to order tests if there are no clear treatment options available.
43 implied HN points 18 Dec 23
  1. About 30% of reagents may be wasted in dead volume on the HiSeq X Flowcell.
  2. The flowcell channels on the HiSeq X have a volume range of 15 to 20 uL.
  3. There could be significant cost implications if reagents costs are a large part of the sequencing expenses.
21 implied HN points 05 Feb 24
  1. NanoString faced financial troubles and declared bankruptcy.
  2. 10X Genomics won a lawsuit against NanoString, impacting their sales and potential for growth.
  3. NanoString's product nCounter platform had limitations and did not bring significant success, leading to their downfall.
36 implied HN points 21 Dec 23
  1. The construction of a flowcell involves specific materials like Kapton KJ and Black Kapton.
  2. Some tests were done on the channel material, showing properties like self-extinguishing and tackiness at high temperatures.
  3. Channels are formed using a piece of cover glass and a section of the flowcell plastic material.
14 implied HN points 03 Mar 24
  1. Several changes are happening at Oxford Nanopore, such as key members leaving the board and the company facing a possible firing of 1/3rd of the staff if revenue doesn't improve.
  2. The anti-takeover shares are set to expire soon, raising questions about the company's future.
  3. Oxford Nanopore's stock price has hit an all-time low, and their earnings report is expected next week, adding more uncertainty.
14 implied HN points 29 Feb 24
  1. NextSeq 550 flowcell has a unique design where the gasket sits on the flowcell interface and the glass is thicker than other instruments, possibly for stability.
  2. The flowcell glass thickness is surprising and might impact the imaging process, requiring specific optics designed for it.
  3. The material of the channel spacer in the flowcell is unknown, leading to curiosity about its composition and potential patent research.
29 implied HN points 04 Jan 24
  1. Sequencers should be as boring and simple as qPCR machines for easy use and accessibility.
  2. Automation in sequencing should focus on sample-to-answer approaches like the GeneXpert in diagnostics.
  3. Broader adoption of sequencing in clinical applications may require a cultural shift towards valuing diagnosis even without immediate treatment options.
29 implied HN points 02 Jan 24
  1. The patents confirm findings from previous teardown and documentation processes.
  2. Negative pressure control is explained by the original location of output wells.
  3. Monitoring pressure carefully is crucial to avoid catastrophic blockages in the system.
29 implied HN points 28 Dec 23
  1. The 10X Chromium Controller component cost is likely less than $5000, significantly lower than its original $35000 price tag.
  2. The key components like Thomas diaphragm pumps range from $200 to $400, making up a portion of the instrument's cost.
  3. Through further cost optimization, it's possible to produce a comparable instrument for much less than $5000.
21 implied HN points 25 Jan 24
  1. Real-time spatial sequencing involves obtaining a full time course of RNA as it's transcribed and cleared from cells.
  2. Challenges include releasing RNA from cells without damaging them, determining porous array density, and developing a sequencing method.
  3. Potential solutions include using electroporation or biological nanopores, adjusting array density, and utilizing real-time sequencing approaches.
80 implied HN points 19 Aug 23
  1. King Flatley ruled the kingdom of Illumina for 17 years, but an evil wizard infiltrated causing chaos.
  2. The evil wizard DeSouza's reign of terror led to the kingdom's downfall as he sought the power of the Holy GRAIL.
  3. Prince Icahn rose to challenge DeSouza, leading to a battle that ultimately determined the fate of Illumina.
43 implied HN points 15 Nov 23
  1. HiSeq X uses an external compute server compared to MiSeq's internal computer setup.
  2. HiSeq X has larger storage volumes in various RAID configurations than MiSeq.
  3. HiSeq X offers about 4x the compute performance of MiSeq, while NovaSeq 6000 is 7 times faster than HiSeq X.