CHICAGO – Cold Spring Harbor Laboratory (CSHL) this week formally introduced a mobile genome sequence analyzer that the Long Island lab — as well as some outsiders — are comparing to the fictional "medical tricorder" device from the 1960s "Star Trek" TV series.
The analysis tool is an iPhone app called iGenomics that works in tandem with portable Oxford Nanopore Technologies sequencers, including the handheld MinIon and the under-development, smartphone-powered SmidgIon. It combines alignment, variant calling, visualization, and annotation into a single application.
"It's this amazing application that can do alignment, variant calling, and visualization entirely on your phone. We think it's super simple so that we've been showing it to other students, other people. I think it has a very gentle learning curve so that in a matter of a minute or two, you can get up to speed with it," said Michael Schatz, associate professor of computer science and biology at Johns Hopkins University, who also holds an adjunct professorship at CSHL.
Schatz is the corresponding author of a paper about iGenomics that was published this week in GigaScience.
"iGenomics uses the same high-performance algorithms for read alignment and variant calling as mainstream software, although iGenomics marks the first time these algorithms have been implemented in a mobile iOS environment," Schatz and colleagues wrote. "Additionally, using the advanced user interface features available in iOS, iGenomics allows for interactive visualization and inspection of the read alignments and variant calls, and contains additional features for reviewing critical mutations of interest."
iGenomics actually is the brainchild of recent University of Pennsylvania graduate and current Facebook software engineer Aspyn Palatnick and Schatz. Palatnick interned in Schatz's laboratory starting when he was a 14-year-old student at Cold Spring Harbor (New York) High School in 2012.
"He had been showing me all the cool games that he had been writing for the iPhone, and I just immediately recognized that he was super talented, a very capable programmer, but wanted to do something a little bit more meaningful than just some fun games," Schatz recalled.
Schatz began educating Palatnick about sequence alignment and variant calling, things he normally taught to his PhD students, and became the young programmer's mentor.
"As the sequencers continued to get even smaller, there were no technologies available to let you study that DNA on a mobile device. Most of the studying of DNA: aligning, analyzing, is done on large server clusters or high-end laptops," Palatnick said in a statement.
Eric Topol, director and founder of the Scripps Research Translational Institute in La Jolla, California, referred to the tricorder idea and noted Palatnick's youth in a tweet sent shortly after the GigaScience paper appeared. "'I've sequenced the #SARSCoV2 of my patient on my iPhone and Air Dropped it to you' (the future) When a high school student invents the 1st DNA tricorder," he wrote.
Indeed, the whole point of mobile apps is to simplify what might otherwise be complex processes and make technology easy to use.
According to the GigaScience paper, iGenomics is shown to be just as fast and accurate as more traditional software like the Burrows-Wheeler Aligner and popular variant callers such as SAMtools and the Genome Analysis Toolkit, though it is not currently suitable for large panels such as whole exomes. "Owing to the lower amount of processing power in mobile devices compared with high-end desktop computers or servers, iGenomics is limited in the size of the genome that can be processed," the researchers wrote.
Schatz sees iGenomics as a way to "democratize" genome analysis because it is freely available to any iPhone or iPad user from Apple's App Store or through Github. It also can work offline, making it particularly suitable for use in remote and low-resource environments, where reliable internet access is scarce.
It will remain open-source technology, according to Schatz.
He said that the "premier application" for iGenomics might be a viral or bacterial genome, something that would take just a few seconds. "In reality, you could do much larger analyses, but from a very practical standpoint, you probably don't want to tie up your phone for minutes to hours to do the alignment overnight," Schatz said.
He said that his group was inspired by the work of Nick Loman at the University of Birmingham in the UK, and others who have taken MinIon sequencers to underserved parts of the world during viral epidemics, including the 2014 Ebola outbreak in West Africa.
"There is a lot of interest to use sequencing in remote parts of the world and beyond," Schatz said. "In addition to democratization of the sequencing, well, here is now a device where we can do this analysis very readily."
Based on a preloaded collection of common known mutations, such as which mutations of the influenza genome cause drug resistance, the iGenomics app can analyze a flu genome in a matter of seconds, even offline. The CSHL team initially included similar information for the SARS-CoV-2 genome, but Schatz said that Apple rejected it on the grounds that too many disreputable app developers are trying to spread false information about the COVID-19 pandemic.
"But we make a tutorial that explains how in a minute or two you can install it anyway," Schatz said.
Schatz's lab has been an early adopter and tester of newer sequencing technology from Pacific Biosciences, Oxford Nanopore Technologies, and 10x Genomics. Notably he was part of Oxford Nanopore's MinIon Access Program going back to 2015, and collaborated with another group at CSHL to sequence and publish the first complete eukaryotic genome with the company's instrumentation, a yeast genome.
"At the time it was very slow and cumbersome and inaccurate, but the nanopore technology has improved tremendously over the last couple of years where now it's very fast, it's efficient, it's very scalable, and the reads are very long," Shatz said.
And some of the hardware is portable, though, as with any sequencer, the Oxford Nanopore MinIon line just outputs raw data.
"For a long time, we've been excited about the portability, but we wanted to make it truly portable, totally accessible to anyone in the world at any time," Schatz said.
"That got us really thinking about, well, wouldn't it be really cool if we had a handheld analysis device? Since we all carry smartphones in our pocket, that seems like a really natural combination," he explained. "It's not that far away, I think, where we really could be carrying around sequencers with us all the time."
With the iGenomics app now out, Schatz said that development is continuing with the addition of new capabilities. "Right now, the analysis always starts from FASTQ files, but the natural thing to do would be to display already prealigned data out of a BAM file so you could do visualization very quickly," he said.
He said that his group would like to beef up downstream analysis, too. "Right now it's good at identifying single nucleotide variants and very small indels, but we'd like to improve the variant calling that's done there," Schatz offered as an example.
Also, the iGenomics team is looking to integrate base calling into the workflow, now that processes have advanced so that base calling no longer has to be performed on high-performance graphics processing units.
"That's something that we're very interested to integrate into the application so you could go completely end-to-end, where you'd have signal data base-called to something like a FASTQ file, align it, variant call it, and visualize," Schatz said.
Schatz also said that he is ready to work with Oxford Nanopore's SmidgIon "the second it is available."
Oxford Nanopore did not immediately respond to a request for comment on iGenomics.