Comment by chrisprobert | Hacker News Reader

Comment by chrisprobert | Hacker News Reader

This article brings up problems with current PCR-based STR genotyping methods, but lacks information about technologies that are competing to be the future of forensic genotyping. Here's some more context on the NGS technologies that are set to replace it:

Illumina is pursuing mitochondrial DNA (mtDNA) sequencing. An advantage here is that cells contain many copies of mtDNA sequences (as opposed to just one copy of each gDNA haplotype), and mtDNA contains hyper-variable regions which confer strong individual specificity. This is potentially advantageous in crime scene samples, where the DNA could be damaged through degradation processes like sun exposure. http://www.illumina.com/areas-of-interest/forensic-genomics/...

Ion Torrent/ThermoFisher are going after the same STR targets, but using their Torrent and Proton NGS platforms (rather than PCR). Unlike regular PCR methods, this can provide things like allele frequency estimates, and can call more than one base into variable regions (which provides more information, and can potentially be used to infer things like height, ethnicity, hair or eye color). https://www.thermofisher.com/us/en/home/industrial/human-ide...

Carlos Bustamante (a Stanford Professor, and world expert in ancient genomics / diverse population genomics: https://med.stanford.edu/profiles/carlos-bustamante) has founded IdentifyGenomics, which is a startup focused on new methods for forensic DNA sequencing (disclosure: I know Carlos, but I'm not involved in his startup).

Definitely an important problem, and will be interesting to who succeeds in converting forensic investigators to use NGS at scale.

Hopefully the underlying use of [mt]DNA in cases also gets some attention and reform. Simply identifying some kind of physical connection is hardly damning; it is inherently circumstantial. It's actually quite rare to finding damning DNA evidence unless the inference directly ties to the crime, i.e. with semen in sexual assault cases or blood in a suspect's car.

It's scary to think prosecutors have been pitching DNA as infallible, damning evidence all along. It means getting a defense attorney off their game might very well lead to an incorrect conviction (think Serial, though obviously the circumstances there are more tied to the use of the cell phone records). I don't think that technology is going to bring us easier convictions for a while yet (e.g. statistical analysis of evidence leading to inference ala Watson might be interesting). Somehow this isn't reflected in how juries have chosen, though, so I think public education about it (even via entertainment) might be the most effective way to change this.

More than that, DNA evidence isn't that difficult to fabricate (Source: http://zidbits.com/2012/06/can-dna-be-faked/). If someone wanted to create fake DNA and leave it at the scene of a crime to frame someone, it wouldn't be all that difficult or expensive (relatively speaking, of course).

It takes some technology that most people don't have (like a centrifuge) but the actual process is simple and can be achieved by anyone with familiarity with the equipment itself.

Totally agree here - would be easy to fabricate DNA oligos with given mtDNA or STR sequences, especially if you know forensic investigators are only going to use very small target sequences for identification purposes.

This could be a case for using shotgun / whole genome sequencing - we'd expect to see a more even distribution of genome coverage than one would get by leaving targeted oligos behind. But this isn't likely to happen anytime soon; the costs are far too high (10-100X greater than targeted sequencing).

In the meantime though, one highly feasible avenue for spotting synthetic DNA oligo fragments is the presence and position of nucleosomes (https://en.wikipedia.org/wiki/Nucleosome), which are DNA-associated protein complexes that occur in DNA from organisms, but not in synthetic DNA oligos. These have been used successfully to trace tissue of origin in cell free DNA in humans, and have specific signals related to chromatin/genome topological state. The only way I can think of to fake this signal would be to have a cell culture from the person you're trying to imitate. Granted, this too is not completely unreasonable - there are now very robust commercially available protocols for deriving iPSCs from small dermal fibroblast samples.

Why would you fabricate DNA when you could just collect some from the target, ala Gattica?

You seem pretty knowledgeable about this stuff. Assuming the businesses you mention plan to provide evidence for use in court, how are they going to reassure the public that they aren't selling crap "forensic science" like we've seen with "bite patterns" in Mississippi?

Good question. This problem affects multiple steps of a NGS-based forensics product: sample collection, DNA extraction, library preparation, the sequencing itself, alignment/assembly, and statistical variant interpretation all have potential for large biases/error modes that could affect the specificity of these types of methods.

One specific answer is that the FBI is gearing up to regulate new devices in this area (https://www.fbi.gov/about-us/lab/biometric-analysis/codis/st...). For example, in this publication (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757157/), they specifically analyze an IonTorrent PGM for use in forensics applications, which we'll probably see them do for various other platforms that come on to the market.

Separately, and outside the forensics realm, there's a trend towards increased regulation of DNA sequencing. For example, NIST has developed/is developing methods to evaluate sequencing platforms: http://www.nist.gov/mml/bbd/dna-022514.cfm. This is relevant to other sequencing applications too (e.g. personalized medicine, somatic tumor profiling, etc). The FDA are also involved here, but more focused on medical applications.

So, I think collectively through both the increase in the forensics community regulating forensics NGS applications, and more broadly the biomedical science/technology community regulating general NGS platforms, we'll see good technology validation standards (at least in the U.S.). But the significantly higher complexity of these systems does introduce more opportunity for error, so it's entirely possible we'll see similar biases in NGS based forensics.

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