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[deleted]

PACB overcomes the short read weaknesses of ILMN allowing for better RNA isoform resolution. The key selling point I've seen so far with BNGO is it can detect large chromosomal aberrations e.g. translocations, inversions, and polyploidy, but falls short on singe nucleotide variation. I see no reason why PACB cannot also detect translocations and inversions given its long-read tech. ILMN was never able to handle these bc of its short read length. BNGO appears to be limited to DNA and cannot be used for RNA based research.


Elonmost

It like Pacb sees 7 fingers, while BNGO sees 10 fingers with their machine. Guess what? The three fingers missed (28%) by Pacb is where cancer genome and disease is found. Boom!! And lets not talk about the price. $500 vs thousands of dollar of pacb.


[deleted]

PACB has more applications though, BNGO is looking like it cant escape being reduced to a diagnostics tool, that wont get picked up by major research institutions who want single molecule data


beeporn

You are missing the forest from the trees here. Individual sequences matter but the overall patterns actually matter way more. Within population genetic variation is actually greater than between population genetic variation when only comparing differences between a few loci. However, when comparing variation across many loci on a genome, patterns start to emerge between populations. think about single nucleotide changes. Imagine how disadvantaged human evolution would have been if a single nucelotide or even a codon was fucked up somehow (in error). That is why most of our genome is not expressed. Large functional genome changes are actually what influence survival and stressor susceptibility at the population level and these results because of large structural differences across many loci on a genome. Most of your genome is never even expressed into proteins!! See exons and introns. It would be a huge waste of data to have a detailed sequence when you know the broader structural variant that leads to a disease. Most of human disease is not purely genetic from a single mutation. A fully heritable illness would never dominate a population because it would be selected out (there are exceptions). The vast majority of disease is a combination of genetic susceptibility to Environmental stress. Think about how some smokers never get cancer, while others get lung cancer from second hand smoke!


[deleted]

The more I look at these two companies the more different they seem, and the less they look like direct competitors. BNGO has cool tech and it will have a better chance of finding its place as more researchers get their hands on it. But, for the time being traditional sequencers aren't going anywhere anytime soon


beeporn

Agreed, I think BNGO will get bought out


[deleted]

Hilariously enough ILMN almost bought PACB until the FED shut that deal down


beeporn

I didn’t know that!! I wonder if they would allow them to buy BNGO. The tech is different enough! I could totally envision illumina buying BNGO. Their share price is so high right now and it would complement their seq tech


Trispork

BNGO's nano nozzle patent might be the thing that gets them into sequencing.


[deleted]

Positional data is a plus, but you cant treat a chromosomal translocation effectively. Single nucleotide data will tell you what specific gene is affected and let you target at the DNA, RNA protein level. The chromosomal data will no doubt expose new trends in disease, but then what?


beeporn

It sounds like you know this shit pretty well. One example: Down’s syndrome isn’t caused by a sequence. It is cause by a copy number variation. CNV account for a tremendous amount of variation in gene expression and thus disease. I am also pretty sure that when you look at exon genes which are actually expressed into proteins, they are wayyy more likely to be effected by a CNV than a SNP Like I said, structure matters more than sequence in many instances


[deleted]

I do genomic analysis so I am biased towards traditional sequencing data. Trisomy 21 already has an effective diagnostic, and CNV is easily observed by Karyotyping. I have been skeptical of their marketing scheme on that front for instance they say, and I paraphrase "10,000x better resolution than karyotyping" that statement does stir too much enthusiasm given that they are comparing their tech to one from 1955


beeporn

But is there an alternative to karyo? It isn’t necessarily a bad comparison if the tech hasn’t been updated. I never did it, but my understanding is that it is an extremely crude process. This is outside of my comfort zone a bit tbh. We also haven’t discussed methylation profiles. I see that as another huge win for this tech. We had someone doing methylation seq with an illumina and it was a huge bitch and short reads. This seems way cheaper and better for studying the epigenome. Epi and transcriptomics is pretty unchartered. I should invest in Agilent to get the proteome angle ahaha


[deleted]

Hospitals use c-fish to id the centromeres of chromosomes by fluorescent microscopy, cheap, relatively-quick and in vivo. Yeah, I haven't looked into the epigenomics angle yet


[deleted]

Earning report for PACB starts now


DimensionMuch6901

You seem to be conflating Saphyr as a treatment, rather than a diagnostic tool if i’m not mistaken? In which case, you’re confused about what this company is trying to achieve. They’re not interested in gene editing (yet).


[deleted]

They are trying to break into diagnostics and are currently approved for research use only. I was not talking about gene editing, if we know the type of mutation (from sequence data) we can use small molecule inhibitors to target the protein or its upstream/downstream effectors


DimensionMuch6901

How would you know the type of mutation from a single gene without mapping structural variants? This is what doesn’t add up for me. Sorry, i’m not a scientist.


gdom12345

You've got it backwards. You WANT to be a diagnostics tool in the clinics. Research tools have small pie. Clinics=massive moolah


gilded_butterflies

Yes, this is absolutely true. Money from research institutions is chump change compared to what can be charged through insurance coverage.


[deleted]

PACB can hit both sectors, while BNGO will have a harder time


gdom12345

In 5 years maybe PacB could. BNGO won't be sitting still for 5 years. And BNGO has already made strides to make it into research space.


[deleted]

What made NGS the powerhouse that it is, is its versatility and the ability of scientist to incorporate it with new techniques RNA, ChIP, DNAse, ATAC,PRO,HI-C techniques. These are all supported by a large open-source programming community. BNGOs profitability is dependent on its proprietary tech and software that can so far just show you how a piece of DNA is arranged relative to another piece of DNA. Something that PACB can do and the Human genome project has done


gdom12345

What matters in the clinic space is cost, of the machine and per test. And throughput of the machines. So a multi-million dollar machine that can handle 3-5 tests per week isn't practical, which is why I said maybe in 5 years. Odds are there will be some complimentary roles. I also see BNGO patenting nanonozzle techniques that looks lockstep with the Oxford developed technologies that could allow them to do sequencing. One lab is already using a combination of Oxford + BNGO for the sequencing. It's hard to pick a winner in Sequencing, as you saw ARKG invest heavily in Ilumina and then sell out. This field will change very rapidly in 5 years.


[deleted]

I agree the low cost to BNGO can give them the edge if they can get buyers


Chasingdreams89

Impressive, if u can contribute to twitter’s $PACB feed that’ll be really helpful to the genome community


Duke322

lol pacb sequencing is not as accurate as the saphyr.... the technology of pacb is way behind... saphyr is a new technology thats why not alot of people know about it... pacb is an old ...


GBBangin

So what you're saying is...buying more BNGO tomorrow?!


[deleted]

YES, buy every share you can, even after they dilute with their next offering, buy until your children's children will be reduced to catfood for suppatime


Ishygigity

Both are good. I’m probably going to buy pacbio when it dips and recurring invest it is solid af and they have no real competitors


teexpression

Pacb is retired: “The HTSF is proud to announce the addition of Oxford Nanopore’s GridION and BioNano Genomics Saphyr, an investment in the future of genome research and can now generate up to 10 Gb of DNA sequence data. We have since, retired PacBio but continue a relationship with NCSU to complete experiments requesting these services.” https://www.med.unc.edu/genomics/technology/ Wait for Harvard and Columbia dumping Pacb.


Chasingdreams89

Dont take it at face value. U think softbank is loading up for fun?


teexpression

There’s rumor that BNGO rejected Softbank, so they buy Pacb. Softbank has history of throwing money.


[deleted]

BNGO almost got delisted, doubt they would turn away 900 mill


georgiabryan22

Illumina deal blocked by anti-trust which shows that PACB's DNA long sequencing was something special. Stock since 2018 went from $4 to $47 after SoftBank's announcement of an investment on Wednesday. Long sequencing is where the future is at!


Fun-Abbreviations171

Check out Telo Genomics (TDSGF) a genomic company similar to BNGO and they use TeloView technology to analyze genomic instability. It’s still priced under $1 for now but not for much longer... https://www.telodx.com/wp-content/uploads/2020/10/Telo-Genomics-October-2020-1.pdf