Skip to main content
Premium Trial:

Request an Annual Quote

Genotyping-Software Startup SoftGenetics Unveils Tool for Pesky Heterozygote Indels


SoftGenetics, a tiny mutation detection-software company based in State College, Penn., has begun selling a tool that helps researchers untangle heterozygote insertion and deletion data points, the company said this week.

The product, which was released to customers in August as a software upgrade, has the potential to save research labs and drug makers time and money, and might further plant the company as a respected niche player.

“We want to find unique niches in the genetic area where we can make a difference — not try to get into the mainstream, but answer problems that the big guys either can’t afford or don’t want to get involved in,” John Fosnacht, a co-founder of the company, told BioInform, SNPtech Reporter’s sister publication, in March.

The software fills a vacuum in mutation-based informatics and plants the start-up more deeply into the niche space. In fact, an impressive list of customers questions the notion that the software is only a niche play.

Accentuate the Positive

Before the addendum to its Mutation Explorer platform was introduced — it is now called Mutation Surveyor — pharmacogenomics researchers at academic research labs and pharmaceutical companies analyzing mutations in heterozygote deletions and insertions were forced to decipher sequence electropherographs with dual-colored lines — a time-consuming and expensive exercise. “What our software does is de-convolutes the dual trace and turns it into two separate traces, and then continues the mutation discovery,” Fosnacht told SNPtech Reporter this week. Fosnacht is also vice president of sales and marketing at SoftGenetics.

The original Mutation Explorer software, which is PC-based, is designed to find rare mutations in specific genes by comparing an individual’s sequence traces to a reference sequence in an electropherograph. “Because it’s not looking at the base text — because that’s just not accurate enough — and it is comparing the actual trace, we have much more sensitivity and accuracy than any of the other competing programs,” said Fosnacht. “What our software does is actually draw the researchers’ attention only to the positive hits, so you don’t have to compare hump to hump.”

The software is around 10 times faster than rival platforms, which include PolyPhred, from the University of Washington; Sequencher, from GeneCodes; and SeqScape, made by Applied Biosystems, according to SoftGenetics. For example, Mutation Surveyor can process around 400 lanes in 120 seconds, which can be as either 400 single-direction sequences or 200 dual-direction sequences, said Fosnacht.

Even a Phred quality score of 20 — which corresponds to 99 percent accuracy and is considered a “high quality” call for sequencing — is not accurate enough for mutation detection, Fosnacht told BioInform in March. “Mutations happen one out of every 1,000 [bases], so what you’re doing when you use their program is using an inaccurate ruler. It just cannot possibly be accurate enough.”

This week, he told SNPtech Reporter that “researchers are satisfied if they can find a mutation that is 20 percent of the primary peak.” SoftGenetics’ program can locate a mutation down to 5 percent. Victor Velculescu, an assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, helped SoftGenetics develop the original software. He said that “at the time we started working with [the company last year], there was basically no good way to do mutation detection electronically. These other programs [PolyPhred, Sequencher, and SeqScape] are in general inadequate, because the sorts of mutations you look for are really often times rare — alterations that occur on the order of one mutation out of a million base pairs of DNA,” said Velculescu.

A 48-lane version of the software sells for around $3,000 to academic labs. The 400-lane version is around $4,500. Existing customers receive 12 months of software upgrades, and the heterozygote update is considered an upgrade. “And since we’ve only been selling for nine months, everybody gets it,” Fosnacht quipped.

Existing customers include genome centers at Harvard Partners, Columbia University, and the Wellcome Trust; academic labs such as Dana Farber, Brigham and Womens, Harvard Institutes of Medicine, and UCLA; big pharma such as Pfizer and Lilly; government labs such as the National Institutes of Health; diagnostic shops such as Quest; and SNP companies such as ParAllele.

The newest version of Mutation Explorer, which was introduced n January, updated a first incarnation that worked only on single-stranded DNA in one direction. The new version is able to process both forward and reverse pairs. The company now has four additional software developers on board and is tackling mutation databasing. Fosnacht said SoftGenetics plans to roll out a product for fragment analysis in two months, and hopes to have software for haplotype analysis ready in eight months.

In the mean time, the Mutation Explorer has become “very popular” for SNP detection, Velculescu said. “Those are easy to detect with this software, but probably are also easy to detect with other existing software. But this still is better because it is more sensitive and more specific.” Velculescu sits on SoftGenetics scientific advisory board, but he does not receive compensation from the company. He said his lab at Johns Hopkins uses sequencing-based technologies to discovery mutations, and does not use a traditional SNP-genotyping tool.

The software “is especially good for identifying new SNPs,” he said. “But if one wants to use it solely for characterizing existing SNPs, there might be certain platforms that might be faster than sequencing-based ones.”

Fosnacht said that the Mutation Explorer is currently being sold to academic hospitals, which use it as an adjunct to traditional clinical diagnostics technologies. He said the platform differs from the Mutation Surveyor in that the Surveyor has some options that enable researchers to manipulate the sensitivity and how it is reported. By comparison, the Explorer platform is fixed. “The user can’t get in there and mess around with it,” he said, adding that this was in part to fulfill the need among clinical diagnostics labs — and eventually the US Food and Drug Administration — for standardized technology.

Customers for the clinical diagnostics application are research-oriented hospitals such as the Mayo Clinic and Johns Hopkins. “They’re using it as a diagnostics technology … as an adjunct to other approved methods,” said Fosnacht. Mutation Explorer is currently sold as a clinical diagnostics tool in The Netherlands, and researchers in the United Kingdom are currently evaluating Mutation Explorer, and will soon decide whether hospitals in that country should use the technology in their labs.

SoftGenetics employs nine people. The $1 million or so Fosnacht said the company currently annualizes as revenues is enough to keep itself afloat without the need for venture capital, though Fosnacht said several new projects may necessitate private equity. “We have a lot more that could be done if we had the cash.” He said he hopes to lock into some cash early next year.

— KL

Filed under

The Scan

Genetic Risk Factors for Hypertension Can Help Identify Those at Risk for Cardiovascular Disease

Genetically predicted high blood pressure risk is also associated with increased cardiovascular disease risk, a new JAMA Cardiology study says.

Circulating Tumor DNA Linked to Post-Treatment Relapse in Breast Cancer

Post-treatment detection of circulating tumor DNA may identify breast cancer patients who are more likely to relapse, a new JCO Precision Oncology study finds.

Genetics Influence Level of Depression Tied to Trauma Exposure, Study Finds

Researchers examine the interplay of trauma, genetics, and major depressive disorder in JAMA Psychiatry.

UCLA Team Reports Cost-Effective Liquid Biopsy Approach for Cancer Detection

The researchers report in Nature Communications that their liquid biopsy approach has high specificity in detecting all- and early-stage cancers.