Massively parallel sequencing

How did that happen?

It is all thanks to Next Generation Sequencing, or NGS.

NGS, okay.

Yeah.

However, advancements in technology have made it possible to analyze trace amounts of DNA quickly and with high accuracy.

Techniques like next-generation sequencing, NGS, have revolutionized the field, allowing for the analysis of degraded or mixed DNA samples.

2.

Cold Case Resurgence

However, advancements in technology have made it possible to analyze trace amounts of DNA quickly and with high accuracy.

Techniques like next-generation sequencing, NGS, have revolutionized the field, allowing for the analysis of degraded or mixed DNA samples.

2.

Cold Case Resurgence One of the most remarkable applications of DNA analysis is its role in reopening cold cases.

They are just looking for a specific product.

library or catalog of infections versus microgen, which is PCR testing, polymerase chain reaction testing with NGS or next generation sequencing, where you have, we're aided by technology and computers and they have a much bigger library of pathogens that they can identify.

So you're much less likely to get something like contaminated sample Mixed microbiota.

Well, yeah, it's mixed.

They tell us whether the HER2 gene itself has been amplified, that is, whether the tumor carries multiple copies of the HER2 gene.

And during the past decade, next-generation sequencing, or NGS, has become increasingly important.

Instead of examining one gene at a time, NGS analyzes hundreds of genes simultaneously.

It can identify mutations, gene amplifications, gene fusions, chromosomal rearrangements, and tumor mutational burden in a single analysis.

Beyond that, whole exome and whole genome sequencing allow even deeper characterization of coding and non-coding regions of the genome.

And that may be come up when we see the material data in first line.

If that trial shows that in first line R2 targeting has a clear impact in metastatic corrector cancer, then I guess that the guidelines may move towards testing really for R2 also upfront in this regard.

How would you do the testing, Lorenza, Florian, in colorectal cancer, NGS, or do an IHC, or do both, or do IHC plus an ISH test in this setting? Any recommendations? Yes.

Oh yeah.

It's also known as Next Generation Sequencing.

It is a fundamental ground up departure from the STR testing we just talked about

aboutOkay, break this down for us because parallel sequencing sounds like, you know, heavy scientific jargon.

No it's not.

And this brings us to the part of our source material that I found the absolute most provocative.

The science to catch ghosts exist today But applying next generation sequencing and hundreds of hours of genealogical research to cold cases is incredibly expensive.

Extremely expensive.

An object at rest stays at rest

Exactly An unsolved case from forty years ago is a statistical liability It takes resources away from active solvable Modern crimes Oh why do it The catalyst for reopening a case like this almost always comes down to a human element colliding with new funding Ah Funding It always comes down to money Often it's a federal cold Case grant being awarded to the county allowing them to finally hire a dedicated detective who only looks at old files Does that make sense Or maybe a new sheriff is elected who makes a big political promise to clear the backlog Alternatively and this happens a lot The lab in Texas might have run an audit of their unidentified remains Oh Like they reached out to Oregon Yeah they might proactively reach out to Oregon saying Hey our technology has crossed a new threshold Send us your worst most degraded samples We can actually read them now But the text specifically mentions them collecting new DNA evidence Right What New evidence They already had the Skull locked in a vault in Texas Qhat are they collecting four decades later A That phrase is doing a lot of subtle work in the AP report It likely refers to two distinct scientific processes Okay What's the first One First they needed a modern reference sample Whatever biological material they might have collected from Theresa's family in Nineteen eighty three or Nineteen ninety seven it was likely gone Degraded or fundamentally incompatible with Twenty twenty four Testing parameters So they needed new Family DNA Yes investigators would have had To locate surviving family members s- siblings perhaps Who are now senior citizens themselves and ask For fresh cheek swabs That has to be an unimaginable emotional shock for the family It really Is I mean you've spent Forty one Years trying to Make peace With the unknown and suddenly a Detective is At your door asking for Your saliva to Match against a Skull found Decades Ago It Completely shatters whatever fragile Closure they Might Have built over those decades You're Reopening the wound completely Okay so that's the family swab Wwhat's the Second part Tthe second Part Of that new Dna Evidence Equation is what Happens In the Lab itself The modern Forensic testing mentioned In the Report is Almost Certainly a Reference to next Generation Sequencing or NGS Next generation sequencing How does that Solve the-- the Shattered Puzzle piece Problem From Nineteen ninety seven Ngs is Just a Technological marvel Remember how The nineties testing Needed Long intact strands yeah The PCR stuff Rght nNext generation sequencing Doesn't need that It is Designed to Read massively parallel Ultrashort fragments of dna Sso it doesn't Care If it's broken Up Exactly iit Can take Those degraded Microscopic shards of Genetic Material Locked inside the Bone matrix Sequence millions of Them simultaneously and use immense computational Power to overlap Them and rebuild the genetic profile Wow I It essentially digitizes the bone Dust and lets an algorithm solve the puzzle That IS wild So science Finally provides the locks Key Science finally caught UP Aaand the Moment that match Is confirmed tThe entire Legal landscape OF THE CASE instantly transforms RIGHT Because a missing Person file THAT'S speculative Very Speculative BUt a legally identified SKULL WITH FORENSIC EVIDENCE OF HOW IT ENDED UP IN THE WOODS THat transitions the Case INTO A definitive homicide INVESTIGATION YES It crosses a legal Threshold Teresa didn't start a NEW LIFE She DIED THERE AND BECAUSE THE ORIGINAL POLICE REPORTS FROM Nineteen eighty THREE DOCUMENT EXACTLY WHO SHE WALKED INTO THOSE woods wITH LAW ENFORCEMENT FINALLY HAS THE FOUNDATION THEY NEED Exactly The corpus delicti requirement is finally satisfied Yeaah They HAVE THE BODY AND THE CIRCUMSTANCES OF ITS DISCOVERY IMPLY FOUL PLAY ThE LEGAL DOMINOES THAT HAD BEEN FROZEN IN PLACE SINCE Nineteen eighty three ARE SUDDENLY CLEARED TO MOVE Which leads Us to thE RAPID ESCALATION IN TWenty twnty five Things move very fast Here THe Ap REPORT STATES THAT LAST YEAR

YEARRelative to the 2026 publication date, Marcus San Fratello is taken into custody.

But he's no longer in rural Oregon.

There were some samples where the tissue identified the mutation and the liquid did not, some that the liquid identified them and the tissue did not, but overall there was really good concordance.

There was also pretty good concordance, around 94%, between NGS and the PCR.

Although NGS was more sensitive than the PCR, but that was a very small difference.

And so it seems that we can use PCR perfectly fine.

And obviously, regardless of what test was being used, ENAVO still outperformed the standard of care arm with placebo.

Yes.

PGT-M, PGT-P, PGT-SR, NGS.

Yes.

SNP array.

I'm gonna describe it, and if you want me to go in deeper, let me know.

I can play with an analogy at the very end.

But I, I think starting with the end acronyms, which was NGS and SNP, I think that's a good starting point because...

Well, actually, I think I wanna go even further back when we're talking about the placenta cells and the cells that become the baby because when we're thinking about embryo screening, that is a good place to start, which is the cells that any embryo screening company receives from an IVF center are coming from cells that become the placenta.