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

Death And NanoString

14 implied HN points • 08 Feb 24
  1. Death can be understood in different categories like reversible/natural or irreversible/catastrophic.
  2. Chapter 11 bankruptcy involves a compromise between a debtor and creditors to reorganize a company.
  3. The concept of a 'forever company' raises questions about the necessity of companies dying for market evolution.

The MiSeq's Excitation LEDs!

21 implied HN points • 02 Nov 23
🔬 Science Specifications Components
  1. The MiSeq instrument by Illumina uses LEDs for excitation, which are cost-effective compared to lasers.
  2. The LEDs used include a photodiode for power monitoring and specific LEDs like the OSRAM green LED and Luminus red LED.
  3. Overall, the LED-based assembly in MiSeq replaces expensive lasers with affordable components, making it a cost-effective solution in sequencing tools.

Singular Spatial Sequencing

14 implied HN points • 06 Feb 24
🕹 Technology Innovation Startups Biotech
  1. Singular Genomics announced a new spatial instrument called G4X for spatial analysis via in situ sequencing using RNA templates.
  2. The G4X technology is similar to 10X Xenium but appears more limited in terms of addressable targets per cell compared to Xenium.
  3. There are concerns about potential patent issues with 10X's spatial patents and ReadCoor IP, raising commercial uncertainties despite the neat research and technology aspects.

An Overview Of The HiSeq X Optical System

14 implied HN points • 15 Dec 23
🔬 Science
  1. The HiSeq X optical system uses TDI imaging to scan across the surface and build up an image line by line.
  2. The system reads out 4 different emission colors which complicates the imaging process.
  3. Various components like ND filters, Powell lens, laser shutter, and dichroic mirror/filter play key roles in enabling accurate imaging on the HiSeq X optical system.
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Repeat Expansions - Long and Short Read Sequencing

14 implied HN points • 11 Dec 23
  1. Repeat expansions can be studied through long and short read sequencing to observe differences.
  2. FMR1 gene on the X chromosome can lead to fragile X syndrome due to repeat expansions.
  3. Sequencing technologies like PacBio provide clearer results for repeat expansions compared to short-read data.

Everything Wrong With: "Illumina: The Measurement Monopoly" Part 4/8

14 implied HN points • 10 Dec 23
🔬 Science Biology Chemistry Physics Engineering Technology
  1. The term 'TechBio' may seem superficial, but technology development in biology is complex and involves a mix of disciplines.
  2. The first qPCR machine from 1992 involved intricate instrumentation like photomultiplier tubes and a variety of electronic components.
  3. The development of technology in biology requires navigating complexity and balancing biochemistry and detection techniques to meet market demands.

Bringing Up An Old EBay MiSeq

14 implied HN points • 06 Dec 23
🔬 Science Biotechnology
  1. Bought an old MiSeq on eBay, faced issues like getting reagents from Illumina and shipping to Japan but managed to resolve them
  2. Had to reset the password for the MiSeq, managed it by using a Linux system to reset and configure passwords
  3. Prepped PhiX control, ran a sequencing run with over-clustered results, but was able to get 20+ bases aligned to PhiX

Let's Buy Singular Genomics!

21 implied HN points • 13 Aug 23
🕹 Technology Genomics Sequencing Instruments Market Research
  1. Singular Genomics is struggling with low share price and few instrument sales.
  2. Proposed solution is to develop a cheap MiSeq-class sequencer to target the lower end of the market.
  3. By focusing on cost-effective instrument with minimal field support, the company aims to attract small labs and researchers.

The MiSeq's Cameras And The Economics of DNA Sequencers

14 implied HN points • 06 Nov 23
🔬 Science Biology Technology Economics Imaging Innovation
  1. DNA sequencers are expensive due to economies of scale, unlike digital cameras that benefit from mass production.
  2. Cheap DNA sequencers could greatly benefit society, but creating them poses technical and sociological challenges.
  3. The cost of components for DNA sequencers, like cameras in the MiSeq, can be broken down to see how much they contribute to the overall expensive price.

Genus Plc And Sex Selection

14 implied HN points • 10 Oct 23
🔬 Science Biotechnology Genetics Agriculture Ethics
  1. Genus Plc focuses on agricultural biotech products, particularly in pig and bovine semen.
  2. They offer Intelligen sexing technologies for selecting the sex of offspring in animals.
  3. The use of similar sex selection technologies in humans raises ethical concerns and has varying levels of effectiveness.

PacBio Market Cap <$1B

7 implied HN points • 18 Mar 24
🕹 Technology Market Analysis Genomics Competitors Sequencing
  1. PacBio's market cap drops below $1B, making it potentially attractive for acquisition.
  2. Despite some positives like new instruments and competitive specs, PacBio faces challenges in gaining traction for long-read sequencing in clinical settings.
  3. The majority of PacBio's IP expires in 2029, raising concerns that competitors could enter the market in the near future.

Everything Wrong With: "Illumina: The Measurement Monopoly" Part 8/8

7 implied HN points • 14 Mar 24
🔬 Science Genomics Biology Technology Business Analysis
  1. The misconception that the author is independently wealthy is addressed, highlighting the need for funding for their content creation activities.
  2. The discussion covers the vertical integration strategies of AffyMetrix and Illumina in the genomics industry.
  3. There is a desire for a less vertically integrated future in the sequencing industry, focusing on filling sequencers with reagents like qPCR machines.

Maybe Nanopore Protein Sequencing Is Easier Than I Thought?... Maybe Not?...

7 implied HN points • 12 Mar 24
🔬 Science Proteomics Sequencing
  1. Protein sequencing can potentially be easier than expected with nanopore technology, allowing for detection of PTMs and obtaining unique fingerprints from proteins.
  2. Proteomics differs from DNA sequencing in that it allows for estimating protein abundance and identifying PTMs in samples, possibly through aligning multiple protein traces.
  3. Challenges in proteomics applications with nanopore platforms include achieving the necessary dynamic range for accurate measurements, which may require advancements in technology.

Is The Revio A Single Color System?

7 implied HN points • 11 Mar 24
🔬 Science Research Technology Innovation Analysis Biology
  1. The Revio possibly uses a single color system for sequencing, which could lead to improved efficiency and simplification of the fabrication process.
  2. The SNR (signal-to-noise ratio) varies significantly between nucleotides in the Revio, indicating potential differences in brightness.
  3. There is ongoing exploration to determine if the Revio sequencing system utilizes a one or two-color system, with a focus on experimental support and additional evidence.

Destroying DNA Sequencers

7 implied HN points • 10 Mar 24
🕹 Technology Security Software Auditing
  1. DNA sequencers can have security vulnerabilities that can be exploited, potentially causing physical damage to the instrument.
  2. Access to the fluidics system in a DNA sequencer could allow for sabotage by manipulating reagents to cause damage.
  3. Careful manipulation of lasers, filter wheels, and motion control components in a DNA sequencer could lead to costly damage, impacting the instrument's functionality.

Illumina's Boring New Sequencer is Boring

29 implied HN points • 30 Sep 22
  1. DNA Sequencers like NovaSeq X are becoming heavier and more boring, signaling reliability and dependability.
  2. Illumina's NovaSeq X introduces incremental developments with a focus on maintaining margins and efficiency in manufacturing.
  3. Despite missed opportunities for more exciting advancements, Illumina is likely to continue with safe, iterative platform developments.

The Utility of Long Reads...

7 implied HN points • 29 Nov 23
  1. Short reads can address a large portion of the human genome efficiently.
  2. Long reads allow us to tackle 5-10% of the genome that short reads alone cannot.
  3. Analyzing genome uniqueness and repeat structure helps evaluate new approaches in genomics.

HiSeq X Cameras and 4 Color Fluorophores

7 implied HN points • 24 Nov 23
  1. HiSeq X cameras use TDI imaging for capturing images.
  2. HiSeq X cameras have two independent sensors each, totaling 4 sensors for 4 color chemistry.
  3. Proper illumination and filtering techniques are crucial to prevent photo-damage in HiSeq X cameras.

Reticula Patent Search Reports!

7 implied HN points • 18 Nov 23
  1. Reticula Patent Search Reports share innovative ideas for single cell sequencing and error rate reduction
  2. Long read single molecule sequencing can improve quality consensus without phasing issues
  3. Original Reticula approach for nucleic acid sequencing uses a novel dye removal method without fluidics

A Qitan Technology Nanopore Data Release

7 implied HN points • 17 Nov 23
  1. Qitan Technology released E.Coli K12 and human cell line datasets under 'Demo Data' on their website.
  2. The read length distribution appears promising, with reasonably long reads.
  3. Q scores from the released data suggest limited calibration to Q25, but show a lower overall error rate compared to previous publications from Qitan.

Oxford Nanopore Error Rate Is >5%?

7 implied HN points • 07 Nov 23
  1. The Oxford Nanopore error rate may be higher than 5%
  2. To find the overall error rate of Oxford Nanopore data, alignment of the data is necessary
  3. Quality scores seem well calibrated up to Q20, but errors rise significantly beyond that

Compute In The MiSeq and Ion Torrent PGM

7 implied HN points • 23 Oct 23
  1. Ion Torrent PGM and MiSeq are similar instruments released around 2010.
  2. They use different technical approaches resulting in different architectures.
  3. The embedded compute in these instruments varies significantly.

Malaria in Maryland

7 implied HN points • 15 Oct 23
  1. A case of Malaria was reported in Maryland, which was initially misdiagnosed as Babesiosis.
  2. Diagnostic testing for diseases like Malaria may require a cultural shift for wider adoption.
  3. There is value in using advanced sequencing-based diagnostic tests, even in unexpected locations like Maryland.

A look inside a MinION Flowcell

14 implied HN points • 07 Dec 22
  1. The post is about a MinION Flowcell.
  2. The content is for paid subscribers only.
  3. The post was removed upon request.

PacBio: All Reads are HiFi Reads? And thoughts on DeepConsensus.

14 implied HN points • 05 Dec 22
  1. Around 50% of reads from PacBio's Sequel IIe are high-fidelity (HiFi), matching the company's marketing data.
  2. PacBio's Revio instrument likely produces only HiFi reads, which is important for the compute requirements of DeepConsensus, taking 200 to 800 hours to run.
  3. The compute requirements for PacBio's DeepConsensus may be a significant cost component for the Revio instrument.

Twinstrand Biosciences

21 implied HN points • 15 Jun 21
  1. Twinstrand Biosciences is a biotech company spinout from the University of Washington with a focus on ultra-high accuracy DNA sequencing.
  2. Their approach involves introducing unique molecular identifiers and strand-defining elements to achieve ultra-high accuracy reads, particularly useful for cancer monitoring and mutations testing.
  3. One major challenge is the significant reduction in throughput due to the need for multiple sequencing passes to ensure accuracy, impacting the practicality of their sequencing method.

Dreampore - Nanopore Protein Sequencing

14 implied HN points • 05 Jul 21
  1. Dreampore is a French Nanopore Protein sequencing company based in Paris.
  2. The technology behind Dreampore involves using a protein nanopore to detect molecules as they pass through, similar to DNA sequencing.
  3. The challenge in protein sequencing with Dreampore lies in distinguishing between different amino acids due to small differences in current blockages and high noise levels.

Mesoscale Diagnostics

7 implied HN points • 19 Oct 21
  1. Mesoscale Diagnostics has high sensitivity immunoassays around 1 fg/ml.
  2. Mesoscale uses electrochemiluminescence to detect antibodies, which has advantages over fluorescence.
  3. Quanterix, Mesoscale, and Roche Cobas have similar sensitivity levels, but Quanterix may have a cost advantage.

Nooma Bio

7 implied HN points • 19 Aug 21
  1. Nooma Bio evolved from TwoPoreGuys and Ontera, maintaining the CEO and CTO.
  2. Their approach of using two nanopores offers advantages like sensing DNA twice and reversing translocation.
  3. The technique may not be suitable for DNA sequencing but shows potential for material sorting applications.

Cees Dekker's protein sequencing paper

7 implied HN points • 28 Jul 21
  1. Cees Dekker's team made progress in nanopore protein sequencing by controlling translocation speed using DNA helicase
  2. Negatively charged peptides were used, demonstrating slower translocation of peptides through nanopores
  3. Single amino acid changes in peptides affect multiple positions, showing promise in protein sequencing development

Nautilus Biotechnology

7 implied HN points • 29 Jun 21
  1. Nautilus Biotechnology was founded in 2016 by Parag Mallick and Sujal Patel.
  2. The company is developing a high throughput single molecule protein fingerprinting platform.
  3. Their approach involves arraying proteins on a surface, using fluorescently labeled affinity reagents for identification, and generating libraries of affinity reagents for use in the process.

Single Molecule Imaging on the Cheap

7 implied HN points • 14 Jun 21
  1. The post discusses building a single molecule imaging instrument for around $500.
  2. Trade-offs like longer exposures and higher laser power may be needed for this setup.
  3. The content is for paid subscribers only.

The NextSeq 550 LEDs And More Dye Experiments

0 implied HN points • 03 Nov 24
🔬 Science Biology Technology Engineering Research Chemistry
  1. The NextSeq 550 uses affordable components like $30 LEDs and image sensors, making it impressive for its cost-effective design.
  2. Experimenting with the LED pinout and driving them at certain voltage and current allowed for practical testing with a spectrometer.
  3. The author shares measurements taken through the NextSeq 550 optical system, indicating a hands-on approach to understanding its functionality.

NextSeq 550 Image Sensor Pinout

0 implied HN points • 03 Dec 24
🕹 Technology Innovation Electronics Imaging Engineering Hardware
  1. The NextSeq 550 has a specific image sensor design that is being explored in detail. Understanding its components can help improve its use.
  2. Previous experiments with LEDs and dyes have provided insights into the image sensor's capabilities. Learning from these tests can enhance the device's performance.
  3. There are various posts that contain helpful observations about the NextSeq 550's imaging and fluidic systems. These notes can serve as valuable references for users and researchers.

Pleno Problems?

0 implied HN points • 02 Dec 24
💼 Business Startups Entrepreneurship Technology Investments Market Trends
  1. Pleno is facing serious problems, including rumors of shutting down and significant staff changes. It's a confusing situation with mixed reports about its future.
  2. The CEO has left the company, which adds to the uncertainty surrounding Pleno. Leadership changes can significantly impact a startup's direction.
  3. A previous investigation into Pleno was based on guesses and patents, highlighting the importance of solid information for making assessments about the company. It's clear that more reliable data is needed to understand their status.

Thoughts On Ultima Genomics...

0 implied HN points • 07 Feb 24
  1. Ultima Genomics focuses on affordability for high throughput users.
  2. Illumina may respond with lower pricing to compete with Ultima Genomics.
  3. PPMSeq by Ultima Genomics offers a promising approach worth monitoring.