Key Takeaways
- Massively parallel sequencing (MPS), also called next‑generation sequencing, generates far more genetic data than traditional STR profiling, enabling identification from minute or degraded DNA samples.
- MPS was pivotal in the arrest of the Golden State Killer by providing a DNA profile that matched a relative in a public genealogy database, launching the forensic investigative genetic genealogy (FIGG) approach.
- The technology helps solve cold cases, differentiate identical twins, and decipher mixed DNA profiles by quantifying each contributor’s share.
- Emerging uses include forensic DNA phenotyping (predicting appearance) and portable, in‑field sequencing (e.g., Oxford Nanopore MinION) for rapid results in remote areas.
- Widespread adoption is hampered by the bioinformatics expertise and computational resources required to interpret large MPS datasets; many labs currently outsource this work.
- Despite challenges, experts agree that MPS represents an inevitable evolution of forensic DNA analysis, complementing rather than replacing STR‑based methods.
Introduction and the Golden State Killer breakthrough
It was the afternoon of April 24, 2018 when Sacramento police arrested 72‑year‑old Joseph DeAngelo, the notorious Golden State Killer, after decades of evading capture. The breakthrough came not from traditional methods but from massively parallel sequencing (MPS), which produced a DNA profile that matched a relative in a public ancestry database. This match enabled investigators to trace DeAngelo through genealogical records, ultimately leading to his arrest for a series of burglaries, rapes, and murders that had perplexed law enforcement for over 30 years.
How MPS differs from STR profiling
The current gold standard for forensic DNA profiling involves extracting DNA, quantifying it, amplifying 21 short tandem repeat (STR) markers via PCR, and separating the products by capillary electrophoresis. This yields a limited “genetic fingerprint” that is compared to a suspect’s profile. MPS begins with similar extraction and quantification steps but then proceeds to library preparation, barcoding, and high‑throughput sequencing on a flow cell. After sequencing—typically two to three days later—bioinformatic analysis reveals thousands of single‑nucleotide polymorphisms (SNPs) or even whole‑genome data, vastly expanding the information available from a single sample.
Sensitivity and utility in challenging samples
Because MPS can detect variation across the entire genome, it excels where STRs fail. For example, distinguishing monozygotic twins requires spotting the ~40‑50 SNP differences that exist between them—a task only feasible with MPS. The technology also works with extremely low DNA quantities; some platforms reliably generate profiles from as little as 25‑50 picograms, meaning a handful of cells can suffice. This sensitivity allows forensic biologists to obtain usable profiles from aged, degraded, or trace‑evidence samples that would give no result with STR‑based methods.
MPS as a complementary tool
Experts stress that MPS does not render STR profiling obsolete; instead, it serves as a complementary approach when traditional methods yield no hits. Laboratories often retain samples that have already undergone STR testing and found no database matches, then apply MPS to the remaining DNA to produce a high‑density profile. This strategy maximizes the value of each piece of evidence while preserving the proven reliability of STRs for routine casework.
Solving cold cases through investigative genetic genealogy
MPS‑derived profiles are uploaded to public genealogy sites such as GEDmatch or FamilyTreeDNA, where they can identify relatives of the unknown contributor. In the Golden State Killer case, the profile matched several third‑cousin relatives; combining these matches with crime‑scene timelines and locations pinpointed DeAngelo. Similar successes have emerged abroad. In New South Wales, Australia, a 2022 review led forensic scientist Alison Sears to use MPS on three historic sexual assaults (1991, 1996, 2002). The analysis showed a single unknown male was likely responsible for all three, and in February 2026 a strike force arrested a 77‑year‑old man identified via a close relative’s DNA match, charging him with multiple offenses.
Challenges: mixed profiles and trace DNA transfer
The heightened sensitivity of MPS can also complicate interpretation. A 2019 experiment demonstrated that a brief handshake can transfer enough DNA for later detection on objects such as a murder weapon, potentially creating mixed profiles that obscure the true source. MPS can quantify the relative contributions of each donor, helping analysts determine which individual is more likely the perpetrator. However, presenting this nuanced evidence in court requires forensic scientists to explain not just “whose DNA is this?” but also “what is the source of this DNA profile, how did it get there, and what proportion belongs to each contributor?” Contextualizing DNA within the broader crime scene narrative remains essential.
Emerging applications: phenotyping and portable sequencing
Beyond identification, MPS supports forensic DNA phenotyping (FDP), where sequenced SNPs are used to predict physical traits such as hair, skin, eye color, or height. While FDP is gaining traction, many laboratories—including Bode Technology—consider it insufficiently validated for routine casework. Another promising development is in‑field testing: devices like the Oxford Nanopore MinION offer a portable, “lab‑on‑a‑stick” MPS platform that can generate results within hours at the crime scene. For victims in rural or remote Queensland, where transporting samples to a central lab may take up to a month, such technology balances access to timely forensic answers across geographic divides.
The bioinformatics bottleneck and infrastructure needs
The primary obstacle to broader MPS adoption is the sheer volume of data it produces, which demands sophisticated bioinformatics expertise and robust computational resources. Many forensic scientists trained in PCR and capillary electrophoresis lack experience handling large datasets, managing CPU‑intensive analyses, or securing adequate storage. As Teresa Vreeland of Bode Technology noted, upskilling through online courses helped, but acquiring suitable hardware and expertise remained a major hurdle. Consequently, many labs outsource MPS work to specialized providers while they build internal capacity.
Outlook: an inevitable transition
Despite current limitations, forensic leaders agree that the shift from capillary electrophoresis‑based STR profiling to MPS is inevitable, though the pace will vary by country, lab, personnel, and funding. Celso Teixeira Mendes Junior emphasizes that the transition will take time but notes there is no viable alternative direction. As more laboratories invest in bioinformatics training and infrastructure, and as portable sequencers become more affordable, MPS is poised to become a routine, powerful component of forensic investigations—solving cold cases, clarifying complex evidence, and ultimately delivering justice where older methods fell short.