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

Top posts of the year

And their main takeaways

Illumina Cluster Domination

29 implied HN points • 29 Jan 24
🔬 Science Genetics Sequencing DNA Research Technology
  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.

Thoughts On Pacific Biosciences

29 implied HN points • 14 Sep 23
🔬 Science Sequencing Accuracy
  1. PacBio's raw accuracy has only slightly improved over 4 generations of instruments.
  2. Fundamental issues, like polymerase kinetics, may be limiting the accuracy of PacBio sequencing.
  3. PacBio has prioritized longer read lengths over accuracy, using cyclic consensus sequencing for improved results.

Some Notes On the MiSeq Flowcell

29 implied HN points • 27 Feb 24
🔬 Science Instruments Construction Materials Research
  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.
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10X Chromium Controller Component Cost Is Likely <$5000

29 implied HN points • 28 Dec 23
🔬 Science Research Technology Innovation Analysis Equipment
  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.

Comments On "An Illumina Sequencer in 2000"

21 implied HN points • 21 Feb 24
🕹 Technology Innovation Biotech Startups Sequencing Acquisition
  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.

Is Oxford Nanopore Failing?

21 implied HN points • 11 Jan 24
💼 Business Finance Technology Growth Failure Market Analysis
  1. Oxford Nanopore has about 3.5 years of cash runway based on their current financial situation.
  2. The company received significant amounts of money outside of product sales which impacted their financial numbers.
  3. Oxford Nanopore's growth trajectory and accuracy claims may not align with their goals of surpassing Illumina in the market.

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.

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.

NanoString Is Dead

21 implied HN points • 05 Feb 24
💼 Business Technology Finance Patents
  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.

Real-time Spatial Sequencing

21 implied HN points • 25 Jan 24
🔬 Science Biology Technology Research Innovation Genomics
  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.

Some Quick Thoughts On The ONT Accounts

21 implied HN points • 06 Mar 24
💰 Finance Analysis
  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.

What The H*ll Is PPMSeq?

21 implied HN points • 17 Feb 24
🔬 Science Biotechnology Genomics Sequencing Bioinformatics
  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.

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.

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.

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.

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

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.

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.

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.

What's Going On At Oxford Nanopore?

14 implied HN points • 03 Mar 24
💼 Business Technology Finance News
  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.

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.

NextSeq 550 Flowcell Notes

14 implied HN points • 29 Feb 24
🔬 Science Research Instruments Materials Optics
  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.

Ultima Unpatterned Flowcells

14 implied HN points • 14 Feb 24
🔬 Science Biotechnology Genomics Technology Research Innovation
  1. Ultima has transitioned to using unpatterned flowcells, which are cheaper and possibly work well with minor drawbacks.
  2. Ultima's manufacturing using unpatterned flowcells involves surface treatment and spin coating to attach and shrink beads for better identification and access.
  3. The occupancy and loading efficiency of Ultima's unpatterned flowcells suggest a potential capacity for 8 billion reads per run, showing advancements since their 2022 preprints.

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.

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.

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.

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

7 implied HN points • 12 Mar 24
🔬 Science 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.

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.

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.

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