Hans Zauner

**This week in *GigaScience*, Hasindu Gamaarachchi and colleagues
published a paper on their [HARU solution for selective
sequencing](https://doi.org/10.1093/gigascience/giad046), to be used
alongside the handheld (["tricorder"
like](http://gigasciencejournal.com/blog/iphone-genomics-beaming-us-up-to-the-tricorder-era/))
Nanopore MinION device**.

With the MinION, it is possible to kick out all non-target DNA strands
before they are processed through the device's pores, thus selectively
sequencing specific target regions of the genome. This is a clever way
to save time and resources, in principle. However, the computational
demands for this method are challenging and usually require an expensive
cluster infrastructure. 

Having a tiny portable sequencer is nice. But the miniaturisation of the
sequencing hardware is not satisfactory if you need bulky and expensive
computers to do the real-time analysis steps that are necessary during a
selective sequencing run.

As Dr.  Gamaarachchi  explains in our
[Q&A](http://gigasciencejournal.com/blog/tag/qa/) below, the authors'
motivation therefore was to realise a portable, open source computer
system that can efficiently perform the analysis tasks of selective
sequencing; in a tiny \$300 device that is "*two times faster than a
30,000 \$ 36-core server, at a fraction of power consumption*".  The
proof-of-concept solution, called HARU, is suitable for small genomes
such as viruses or bacteria, but the authors hope that their work will
lead to further improvements down the line: "*Our dream would be to one
day have a chip within a nanopore sequencer that can handle the
computational requirement of selective sequencing directly.*",
Gamaarachchi concludes.

## **Author Q&A with Hasindu Gamaarachchi** {#author-qa-with-hasindu-gamaarachchi .wp-block-heading}

### ***"What is selective nanopore sequencing and how does it work"?*** {#what-is-selective-nanopore-sequencing-and-how-does-it-work .wp-block-heading}

Selective nanopore sequencing is a nascent method to perform rapid
genome analysis that enables the sequencing of specific genomic "regions
of interest" rather than the entire genome. This programmable approach
is free from biochemical processes, making it highly flexible and
cost-effective.

::: {.wp-block-image}
<figure class="alignleft size-medium is-resized">
<img
src="http://gigasciencejournal.com/blog/wp-content/uploads/2023/07/author-300x282.jpg"
class="wp-image-5022" loading="lazy" decoding="async"
srcset="http://gigasciencejournal.com/blog/wp-content/uploads/2023/07/author-300x282.jpg 300w, http://gigasciencejournal.com/blog/wp-content/uploads/2023/07/author.jpg 422w"
sizes="(max-width: 225px) 100vw, 225px" width="225" height="212" />
</figure>
:::

Nanopore sequencers utilise an array of tiny pores, known as nanopores,
to measure and record fluctuations in ionic current as DNA/RNA strands
pass through them. If the region is irrelevant to the given research
problem, the voltage across the nanopore can be reversed to eject the
DNA/RNA strand from the pore. This approach optimises sequencing time
and consumable resources (flowcells) by focusing primarily on the
regions of interest.

### ***"What are application examples for selective sequencing?"*** {#what-are-application-examples-for-selective-sequencing .wp-block-heading}

Selective sequencing can reduce the time and cost of sequencing in
applications such as genetic disease diagnosis, cancer detection, the
surveillance of viruses (e.g. SARS-CoV-2) and other pathogens, and
sequencing low abundance species in an environmental sample containing
thousands of species. For example, it has been recently demonstrated
that nanopore selective sequencing can be used to create a [single test
for over 50 genetic diseases that will cut diagnosis cost and
time.](https://www.science.org/doi/10.1126/sciadv.abm5386)

### ***"What are the technical and computational challenges that come with this method?"*** {#what-are-the-technical-and-computational-challenges-that-come-with-this-method .wp-block-heading}

The real-time analysis of the data streamed from the sequencer is
computationally demanding. The rapid analysis of data from hundreds of
nanopores is crucial to promptly identify and eject unnecessary DNA/RNA
strands. Any delay in this processing would undermine the effectiveness
of selective sequencing. While nanopore sequencers like the Oxford
Nanopore MinION are small portable devices comparable in size to a
mobile phone and powered via USB, the computer required for performing
selective sequencing is typically the size of a non-portable small
fridge, consuming power that is hundreds of times greater than the
MinION.

::: {.wp-block-image}
<figure class="aligncenter size-full is-resized">
<img
src="http://gigasciencejournal.com/blog/wp-content/uploads/2023/06/HARU.jpg"
class="wp-image-4985" loading="lazy" decoding="async"
srcset="http://gigasciencejournal.com/blog/wp-content/uploads/2023/06/HARU.jpg 815w, http://gigasciencejournal.com/blog/wp-content/uploads/2023/06/HARU-300x189.jpg 300w, http://gigasciencejournal.com/blog/wp-content/uploads/2023/06/HARU-768x484.jpg 768w"
sizes="(max-width: 611px) 100vw, 611px" width="611" height="386" />
</figure>
:::

### ***"What was your motivation to work on this problem"?*** {#what-was-your-motivation-to-work-on-this-problem .wp-block-heading}

The usefulness of the nanopore MinION as a portable device is negated if
it depends on a computer which is non-portable. Although nanopore
selective sequencing has the potential to revolutionise diagnostic
techniques in the future, it necessitates portable computational
solutions to be utilised in settings such as clinics. Our motivation was
to realise a portable computer system that can efficiently do the
analysis side of the selective sequencing, which is synergistic with the
size of the MinION.

### ***"What is the main advance of your solution, HARU?"*** {#what-is-the-main-advance-of-your-solution-haru .wp-block-heading}

HARU is a complete system that works on off-the-shelf devices, as
opposed to being a conceptual work limited to simulation. In other
words, it is a tangible prototype that actually runs. The full proposed
design is available open-source. We have pre-compiled binaries and
step-by-step instructions on building the overarching HARU system from
scratch. One can simply purchase Xilinx's Kria AI Starter Kit, flash the
device, and execute HARU.

Advantages of HARU include portability, low cost, high-processing
throughput, low power consumption and scalability. HARU can also be used
as a framework for other future work intending to explore acceleration
for selective sequencing on hardware.

### ***"What about the costs? How much would it cost to implement the software/hardware setup as presented in the article?"*** {#what-about-the-costs-how-much-would-it-cost-to-implement-the-softwarehardware-setup-as-presented-in-the-article .wp-block-heading}

The only cost to replicate the HARU system is the target board itself.
The software is free and open-source. We target Xilinx's Kria AI Starter
Kit, which is currently retailed at \$300. As we have shown in the
paper, for selective sequencing based on the algorithm called
subsequence Dynamic Time Warping, this tiny \$300 device is 2X faster
than a 30,000\$ 36-core server, at a fraction of power consumption.

### ***"Is this a one-off proof of concept, or are there plans to develop this system for routine use?"*** {#is-this-a-one-off-proof-of-concept-or-are-there-plans-to-develop-this-system-for-routine-use .wp-block-heading}

While HARU is currently a proof-of-concept, we envision continuing
development and integration of this system into the nanopore sequencing
ecosystem for routine use. However, this is a long journey as a lot of
development has to be conducted to interface with the nanopore sequence
acquisition and control software (closed source) called MinKNOW. Also,
HARU is currently only suitable for small genomes such as viruses or
bacteria and is impractical for large genomes like the human genome. We
have thoughts to combine HARU with fast index-based mapping methods to
tackle the problem with such large genomes. Open-sourced HARU can be
used as a stepping stone by other researchers who would like to explore
methods of hardware acceleration for selective sequencing.  Our dream
would be to one day have a chip within a nanopore sequencer that can
handle the computational requirement of selective sequencing directly.

#### References {#references .wp-block-heading}

**Efficient real-time selective genome sequencing on
resource-constrained devices**  
Po Jui Shih, Hassaan Saadat, Sri Parameswaran, Hasindu Gamaarachchi  
GigaScience, Volume 12, 2023, giad046,
<https://doi.org/10.1093/gigascience/giad046>

Source code for the HARU accelerator: <https://github.com/beebdev/HARU>

The post [Selective sequencing on a shoestring: the \$300 HARU
system](http://gigasciencejournal.com/blog/selective-sequencing-on-a-shoestring-the-300-haru-system/){rel="nofollow"}
appeared first on
[GigaBlog](http://gigasciencejournal.com/blog){rel="nofollow"}.


<strong>
 This week in
 <em>
  GigaScience
 </em>
 , Hasindu Gamaarachchi and colleagues published a paper on their HARU solution for selective sequencing, to be used alongside the handheld (“tricorder” like) Nanopore MinION device
</strong>
.   With the MinION, it is possible to kick out all non-target DNA strands before they are processed through the device’s pores, thus selectively sequencing specific target regions of the genome.

Selective sequencing on a shoestring: the $300 HARU system

Scott Edmunds

*The first comprehensive mobile genome analysis application, iGenomics,
is now available for download and use on an iOS smartphone*. *By pairing
an smartphone with a handheld DNA sequencer, users will be able to
create a mobile genetics laboratory, reminiscent of the Star Trek's
"tricorder".*

<figure class="wp-block-image size-large">
<img
src="http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1-1024x575.jpg"
class="wp-image-3640" loading="lazy" decoding="async"
srcset="http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1-1024x575.jpg 1024w, http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1-300x168.jpg 300w, http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1-768x431.jpg 768w, http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1-1536x863.jpg 1536w, http://gigasciencejournal.com/blog/wp-content/uploads/2020/12/portable_sequencing_smaller-1.jpg 1820w"
sizes="(max-width: 1024px) 100vw, 1024px" width="1024" height="575" />
</figure>

[Just published](https://doi.org/10.1093/gigascience/giaa138) is an
article presenting  iGenomics, the first DNA sequencing toolkit that can
run on a smartphone. The work carried out by researchers at Cold Spring
Harbor Laboratory takes us one step closer to making the tricorder
envisioned by Star Trek a reality. While hand-held DNA sequencers have
been available since 2014 (an event marked by our Data Note of the
[first complete *E. coli*
genome](https://doi.org/10.1186/2047-217X-3-22) sequenced by a handheld
nanopore sequencer), an equally simple and portable analysis platform
has not been available until now. We've previously showcased studies
[sequencing biodiversity in the
jungle](http://gigasciencejournal.com/blog/dna-day-2019-how-to-sequence-non-model-organism/),
but this still required a backpack of computer and other gear. iGenomics
takes this a step further by providing applications to align reads, call
variants, and visualize the results entirely on an iOS smartphone.

The project that led to iGenomics started out as a high school
internship at Cold Spring Harbor Laboratory in New York State, when
[*GigaScience* Editorial Board
Member](https://academic.oup.com/gigascience/pages/Editorial_Board)
Professor Michael Schatz noted the brilliance of a young high school
student, Aspyn Palatnick.

Aspyn says of how the project got started: "In junior high school, I
spent a lot of time making iOS apps, mainly games with fun interfaces.
When I was 14, I started interning under Mike and he taught me the ropes
of DNA sequence alignment and analysis. At some point, Mike had the
realization that with my iOS app making skills and his mentorship, we
could work together to build a solution in this space."

<figure
class="wp-block-embed is-type-rich is-provider-twitter wp-block-embed-twitter">
<div class="wp-block-embed__wrapper">
<blockquote>
<p>"I've sequenced the <a
href="https://twitter.com/hashtag/SARSCoV2?src=hash&amp;ref_src=twsrc%5Etfw">#SARSCoV2</a>
of my patient on my iPhone and Air Dropped it to you" (the future)<br />
When a high school student invents the 1st DNA tricorder<a
href="https://t.co/1RZ0L7Yk1k">https://t.co/1RZ0L7Yk1k</a> <a
href="https://twitter.com/AspynPalatnick?ref_src=twsrc%5Etfw">@AspynPalatnick</a>
<a
href="https://twitter.com/mike_schatz?ref_src=twsrc%5Etfw">@mike_schatz</a>
<a
href="https://twitter.com/GigaScience?ref_src=twsrc%5Etfw">@GigaScience</a>
<a href="https://twitter.com/nanopore?ref_src=twsrc%5Etfw">@nanopore</a>
<a href="https://t.co/I5Dnv9NbhK">pic.twitter.com/I5Dnv9NbhK</a></p>
<p>— Eric Topol (@EricTopol) <a
href="https://twitter.com/EricTopol/status/1335949572934287365?ref_src=twsrc%5Etfw">December
7, 2020</a></p>
</blockquote>
</div>
</figure>

Analysing genomes on a phone is intuitively different from doing so on a
computer. A phone app requires a suitable graphical user interface with
touch-related functions that are natural to anyone who has ever used a
touch screen mobile device. For carrying out its analyses,
[iGenomics](http://​http://schatz-lab.org/iGenomics/​) also has an option
to export mutations and analysis data via email, Dropbox, Airdrop, or
sharing via installed apps such as Google Drive.

Aspyn describes the potential uses for an app of this type: "We've
targeted iGenomics towards the analysis of small viral genomes like
influenza. Given this, with the support of Elodie Ghedin, we've used
iGenomics for identifying which mutations in a strain of influenza would
signal a resistance to particular antivirals. In simpler terms, we've
demonstrated that iGenomics could be used to determine which drug
classes would be ineffective in treating influenza."

Another important use case of iGenomics was carrying out the first
analysis of coronavirus mutations within a few seconds. To support this
capability, the authors have [provided a
tutorial](http://​http://schatz-lab.org/iGenomics/​) using the tool to
compare the first published SARS-CoV2 patient and the consensus genome
from a bat SARS-like coronavirus isolate (MG772934.1/).

Aspyn describes the potential uses for an app of this type: "We've
targeted iGenomics towards the analysis of small viral genomes like
influenza. Given this, with the support of Elodie Ghedin, we've used
iGenomics for identifying which mutations in a strain of influenza would
signal a resistance to particular antivirals. In simpler terms, we've
demonstrated that iGenomics could be used to determine which drug
classes would be ineffective in treating influenza."

Aspyn adds on the portability side: "iGenomics solves the software-side
of shifting the genomics field to be mobile; the final piece for
completely portable DNA analysis is a sequencer that can read DNA
directly into a mobile device and perform basecalling. iGenomics already
has support for importing reads and references from external apps so, as
soon as a mobile sequencer exists, iGenomics can take advantage of it
right away. Oxford Nanopore has been [actively working on a mobile
sequencer](https://nanoporetech.com/products/smidgion) for the past few
years so we expect these to be available to the public in the not too
distant future."

Supervisor of the project Professor Michael Schatz adds: "iGenomics has
been in our culture for decades, ever since we saw Dr. "Bones" McCoy use
a tricorder to get an instant readout of the DNA and other molecules
around him on Star Trek. iGenomics makes a really important step forward
towards making this real by allowing for the analysis of viruses and
microbes within a few seconds all on your iPhone. And while the concept
has been around for several decades, it took Aspyn's brilliance and
creativity to make it come to life all within an easy-to-use app."

iGenomics is open-source and available for free on Apple's App Store:
[https://apple.co/2HCplzr​](https://apple.co/2HCplzr%E2%80%8B)

A youtube video of Aspyn Palatnick presenting the tool is available in
our [youtube channel](https://www.youtube.com/c/GigaScienceJournal).

<figure
class="wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio">
<div class="wp-block-embed__wrapper">
<div class="iframe">
<div id="player">

</div>
<div class="player-unavailable">
<h1 id="ein-fehler-ist-aufgetreten." class="message">Ein Fehler ist
aufgetreten.</h1>
<div class="submessage">
<a href="https://www.youtube.com/watch?v=Kpymh2-JXzw"
target="_blank">Sieh dir dieses Video auf www.youtube.com an</a> oder
aktiviere JavaScript, falls es in deinem Browser deaktiviert sein
sollte.
</div>
</div>
</div>
</div>
</figure>

## **R**eferences {#references .wp-block-heading}

Aspyn Palatnick, Bin Zhou, Elodie Ghedin, Michael C. Schatz. iGenomics:
Comprehensive DNA Sequence Analysis on your Smartphone. *GigaScience*,
Volume 9, Issue 12, December 2020, giaa133
<https://doi.org/10.1093/gigascience/giaa138>

The post [iPhone Genomics: beaming us up to the "tricorder"
era](http://gigasciencejournal.com/blog/iphone-genomics-beaming-us-up-to-the-tricorder-era/){rel="nofollow"}
appeared first on
[GigaBlog](http://gigasciencejournal.com/blog){rel="nofollow"}.


<em>
 The first comprehensive mobile genome analysis application, iGenomics, is now available for download and use on an iOS smartphone
</em>
.
<em>
 By pairing an smartphone with a handheld DNA sequencer, users will be able to create a mobile genetics laboratory, reminiscent of the Star Trek’s “tricorder”.
</em>
Just published is an article presenting  iGenomics, the first DNA sequencing toolkit that can run on a smartphone.

Rogue Scholar Posts

Selective sequencing on a shoestring: the $300 HARU system

iPhone Genomics: beaming us up to the “tricorder” era