index.Rmd

---
title: ".large[The disruptive nature of portable sequencing & edge compute for community empowerment]"
author:  |
  | Nvidia GTC, 12<small><sup>th</sup></small> - 16<small><sup>th</sup></small> April 2021
  | .large[<b>Dr Miles Benton</b>]
  |
  | <b>Human Genomics</b>
  | <b>Institute of Environmental Science and Research [(ESR)](www.esr.cri.nz)</b>
  | <b>Aotearoa</b> (New Zealand)
date: 
output:
  xaringan::moon_reader:
    css: "libs/remark-css/example_mod.css"
    lib_dir: libs
    nature:
      highlightStyle: github
      highlightLines: true
      countIncrementalSlides: false
      ratio: 16:9
editor_options: 
  chunk_output_type: console
---
class: middle hide_logo

```{r setup, include=FALSE}
options(htmltools.dir.version = FALSE)
options(knitr.table.format = "html") 
# require(DT)
xaringanExtra::use_xaringan_extra(c("tile_view", "animate_css", "tachyons", "panelset"))
xaringanExtra::use_webcam(width = 1100, height = 800)
```

```{r xaringan-logo, echo=FALSE}
# use logo
xaringanExtra::use_logo(
  image_url = "https://upload.wikimedia.org/wikipedia/commons/6/66/ESR_SFC_logo.png",
  width = "138px",
  height = "87px",
  position = xaringanExtra::css_position(bottom = "1px", right = "1.5em"),
  link_url = "https://www.esr.cri.nz/",
  exclude_class = c("title-slide", "inverse", "hide_logo")
)
```

# .center[Advocates for reproducible research...]

## .center[Where possible all presentations and code are available online]

<br />

<p>
.center[
<img src="images/github_logo.png" style="width: 520px; margin-right: 1%; margin-top: 1.5em;"/>
<img src="images/sirselim_qrcode.png" style="width: 202px; margin-right: 1%; margin-top: 1.5em;"/>
]
</p>

<br />

.center[[sirselim.github.io/presentations](http://sirselim.github.io/presentations)]

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  </a>
</footer>

---
class: middle

# Who are we?

.pull.right[
.large[<span style="color:#3498DB">**You may have seen recently**...</span>]
]

---
class: top

# Genomics in NZ's pandemic response

### A sequencing success story made possible by the awesome [**Una Ren**](https://twitter.com/sciolato), [**Matt Storey**](https://twitter.com/mathstorey) & [**Joep de Ligt**](https://twitter.com/joepdl)

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/JN_FirstGenome.PNG" style="width: 80%; margin-right: 1%; margin-top: 0em;"/>
  </div>
  <div class="fl w-40 bg-white tc">
    <p style="text-align:center"> Give us some time and money and we'll demonstrate what this technology can do. <br />  <br />  <br /> </p>
  </div>
  
  <div class="fl w-40 bg-white tc">
    <img src="images/NZChiefSCIAdvisor.PNG" style="width: 100%; margin-right: 1%; margin-top: 0em;"/>
  </div>
</article>

---
layout: false
class: middle inverse

background-image: url("https://cdn.vox-cdn.com/thumbor/llQlREwACaitewdPcLm5HzWT_g0=/0x1:1100x734/920x613/filters:focal(0x1:1100x734):format(webp)/cdn.vox-cdn.com/imported_assets/1507663/DNA-sequence.jpg")
background-size: cover

.massive[**Genomic sequencing**]

???

DNA - A, T, C, G
Part of all 'living' things

---

# A snapshot of the Human Genomics group

* **Independent research**
  * type-2 diabetes & obesity (genomics, epigenetics, protein 'omics)
  * Guinea pigs! (<span style="color:#3498DB"><b>Max Berry, University of Otago</b></span>)
  * empowering people to explore and interpret their data

<br>

* **Clinical diagnostics through genetics**
  * Contract(s) with CCDHB <span style="color:#3498DB"><b>Wellington Regional Genetics Lab</b></span>
  * Providing support to CCDHB for Clinical Genomics GA project (<span style="color:#3498DB"><b>Stephen Robertson</b></span>)

<br>

* **Clinical research**, in collaboration with local clinician (<span style="color:#3498DB"><b>Richard Carroll</b></span>) - hyperparathyroidism
  * sequencing 100 exomes
  * engaging clinicians from other DHBs
  * exploring the replacement of gene panels with exome/genome

---
class: middle center

# A big part of what we do is sequencing

.center[<img src="images/dna_hackers.jpg" style="width: 30%; margin-right: 1%; margin-top: 0em;"/>]

---
layout: false
class: middle

<p>
.center[
<img src="https://www.illumina.com/content/dam/illumina-marketing/images/decade-in-sequencing/decade-in-sequencing-320-web-graphic.jpg" style="width: 820px; margin-right: 1%; margin-top: 1.5em;"/>
]
</p>

.small[.center[
(image source: [illumina.com](https://www.illumina.com/techniques/sequencing/dna-sequencing.html))
]]

???

I used the word portable in my previous slide, this is not a phrase one would attribute to machines from Illumina / PacBio.

These things are huge! ... and expensive.

---
class: middle

> *"Soon, It Will Cost Less To Sequence A Genome Than To Flush A Toilet -- And That Will Change Medicine Forever"*

<p>
.center[
<img src="images/seqCost.png" style="width: 620px; margin-right: 1%; margin-top: 1.5em;"/>
]
</p>

.small[.center[
(image source: [https://www.businessinsider.com.au/super-cheap-genome-sequencing](https://www.businessinsider.com.au/super-cheap-genome-sequencing-by-2020-2014-10))
]]

---
class: top

# Can we speed things up?

<b>Thanks to eResearch 2020<b> ...enter [Nvidia Clara Parabricks](https://www.nvidia.com/en-us/docs/parabricks/)

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/parabricks.png" style="width: 40%; margin-right: 1%; margin-top: 0em;"/>
  </div>
  <div class="fl w-50 bg-white tc">
    <img src="images/nvidia.png" style="width: 50%; margin-right: 1%; margin-top: 1.5em;"/>
  </div>
</article>

.center[<span style="color:#3498DB"><b> powered by GPU </b></span>]

.center[<img src="images/tesla_v100.jpg" style="width: 30%; margin-right: 1%; margin-top: 0em;"/>]

---
class: middle

.center[
<img src="images/parabricks_pipelines.png" style="width: 70%; margin-right: 1%; margin-top: 0em;"/>
]

<br>

.center[[www.nvidia.com/en-us/healthcare/clara-parabricks/](https://www.nvidia.com/en-us/healthcare/clara-parabricks/)]

---

# How much does that matter?

### Identical pipelines with a slight difference...

<article class="cf">
  <div class="fl w-100 w-50-ns bg-white">
    <ul>
    <li><b>Pipeline [CPU]</b></li>
      <ul>
        <li>Exomes: >100X exome takes between 8-12 hours</li>
        <li>Genomes: ~30X genome takes between 30-48 hours</li>
      </ul>
    </ul>
    <br>
    <ul>
    <li><b>Pipeline [GPU - Parabricks]</b></li>
      <ul>
        <li>Exomes: >100X exome takes between <span style="color:#3498DB"><b>6-12 mins</b></span></b></li>
        <li>Genomes: 100X genome takes <span style="color:#3498DB"><b>~4 hours</b></span></li>
      </ul>
    </ul>
  </div>
  <div class="fl w-100 w-50-ns bg-white tc">
    <img src="images/fast-turtle.png" style="width: 70%; margin-right: 1%;"/>
  </div>
</article>

---
class: middle

# Another type of sequencing technology

.pull-right[...sorry PacBio I'm ignoring you today...]

---
layout: false
class: middle

<p>
.center[
<img src="https://cdn-a.william-reed.com/var/wrbm_gb_food_pharma/storage/images/publications/food-beverage-nutrition/foodnavigator.com/article/2018/03/21/oxford-nanopore-raises-funds-to-support-commercial-expansion/7992741-1-eng-GB/Oxford-Nanopore-raises-funds-to-support-commercial-expansion_wrbm_large.jpg" style="width: 620px; margin-right: 1%; margin-top: 1.5em;"/>
]
</p>

.small[.center[
(image source: [nanoporetech](https://nanoporetech.com/about-us/news/oxford-nanopore-announces-ps100-million-140m-fundraising-global-investors))
]]

???

flongle: ~$500 USD for 5
1 might be enough for a metagenome

minION: $1000 

smidgION: still just a concept

gridION: ~$50K

promethION: ~$230K

---
layout: false
class: hide_logo

background-image: url("images/david_slide.png")
background-size: contain

<a href="https://f1000research.com/slides/8-1947" style="position:absolute; top:625px; left:190px">slide kindly supplied by David Eccles (f1000 presentation)</a>
<a href="https://www.youtube.com/watch?v=CHCAb-PAqUI" style="position:absolute; top:652px; left:190px">"Sequencing DNA with Linux Cores and Nanopores"</a>

???

David's talk and a live demo are linked.

---
layout: false
class: middle hide_logo

<center>
<iframe width="1000" height="562" src="https://www.youtube.com/embed/RcP85JHLmnI" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>
<br />
&copy; Oxford Nanopore Technologies
</center>

---
layout: false
class: middle

# Example squiggle plot

![](https://nanoporetech.github.io/tombo/_images/single_samp.png)

.small[.center[
(image source: [tombo manual](https://nanoporetech.github.io/tombo/plotting.html))
]]

???

What we 'see' when DNA passes through the pores.

---
class: middle

# GPUs accelerate basecalling of Nanopore long-read data (a lot)

.center[
<img src="images/gpu_magic.jpg" style="width: 110%; margin-right: 1%; margin-top: 1em;"/>
]

<br>

.center[
Nanopore basecalling benchmarking: [link (ESR GitHub)](https://esr-nz.github.io/gpu_basecalling_testing/gpu_benchmarking.html)
]

---
class: middle

# Why GPUs?

.pull-left[
New type of sequencing data requires new type of 'analysis'

* squiggle data lends itself nicely to neural nets
* GPUs are very capable in this space
  - CUDA cores


ESR GPU basecalling benchmarks [(link)](https://esr-nz.github.io/gpu_basecalling_testing/gpu_benchmarking.html)
* Titan RTX & 2x Tesla V100
]

.pull-right[
![Titan RTX](images/titan.jpg)
]

<br>

.small[.center[
[UPDATE:] guppy is now able to scale across multiple GPUs!
]]

---
class: middle

# Let's step back a couple of years 

.pull.right[
.large[<span style="color:#3498DB">... **a personal story** ...</span>]
]

---
class: middle

<p>
.center[
<img src="images/jamie_sm.jpg" style="width: 330px; margin-right: 1%; margin-top: 1.5em; border: 3px solid white;"/>
<img src="images/jamie_big.jpg" style="width: 334px; margin-right: 1%; margin-top: 1.5em; border: 3px solid white;"/>
]
</p>

---
class: top

# a personal story

.large[
<br>

* had a lumbar puncture ('9 days' old) 
  * (after being born 8 weeks early)

<br>

* suspected meningitis (bacteria/viral)?
 * told after the fact

<br>

* \>**48 hours** for results return

]

---
class: top

# a personal story

.large[
... imagine a more ‘real-time’ procedure:
]

<br>

--

.large[
* a sample (i.e. blood) taken,
* DNA/RNA extracted/enriched,
* sequencing library prepared,
* nanopore sequencing initiated,
* sequence starts coming in almost instantly,
* **<span style="color:#3498DB">time to first read-match detection <1 hr</span>**

]

--

<br>

.center[.huge[
**This isn't a stretch of the imagination anymore, soon to be reality**
]]

???

Stress how fast and low cost this has the potential to be.

---
class: top

# what are we doing?

.large[
Portable ‘real-time’ sequencing for the masses?
]

--

* <span style="color:#3498DB">**the idea**</span>

  * low cost (< many mobile phones)
  * accessible
  * portable
  * robust (...may have "performed" a drop test...)
  * fun!

--
  
* <span style="color:#3498DB">**example use cases**</span>

  * field sequencing (real-time monitoring, forensics, agriculture, waterways, ...)
  * **clinical settings**
  * community outreach / teaching

--

.center[
Community Science | "United in Data"
]

---
class: middle

# Our experiences with the Xavier [(link)](https://hackmd.io/@Miles/HkumH7sBH)

.pull-left[.right[
<img src="images/IMG_20191021_165639.jpg" style="width: 200px;"/>
<img src="images/IMG_20191025_094614.jpg" style="width: 200px;"/>
]]

.pull-right[.left[
<img src="images/battery_charge.jpg" style="width: 200px;"/>
<img src="images/xavier_in_use.jpg" style="width: 200px;"/>
]]

.center[
<img src="images/jetson_xavier_jtop_screenshot.png" style="width: 650px;"/>
]

???

Talk about the Xavier specs:

 * 8 core arm 
 * 16 GB of RAM
 * 512 CUDA core and 64 tensor cores
 * 512 GB SSD NVMe

---
class: top

# Benchmarking [(link)<sup>*</sup>](https://gist.github.com/sirselim/2ebe2807112fae93809aa18f096dbb94)

.small[
\* spoilers for those following along live
]

--

<br>

Most Jetson devices have the ability to be put into different power modes

<br>

```{r, echo=FALSE}
tflops <- read.delim('power_table.txt', head = T, as.is = F)
# knitr::kable(tflops, 'html')
DT::datatable(
  head(tflops, 10),
  fillContainer = FALSE, rownames= FALSE, options = list(dom = 't')
)
```
.small[
***Note:*** this table represents basecalling performed when running on a portable powerbank.
]

???

Why is 10W mode exciting?

We're running in 30W MAX mode for this live demo - running on a portable powerpack.

---
class: top

## Very rough comparison of Nvidia ecosystem<sup>#</sup>

```{r, echo=FALSE}
tflops <- read.delim('tflop_table.txt', head = T, as.is = F)
# knitr::kable(tflops, 'html')
DT::datatable(
  head(tflops, 10),
  fillContainer = FALSE, rownames= FALSE, options = list(dom = 't')
)
```

.small[Price in USD]  
.small[<sup>#</sup> a very small selection of what Nvidia offers obviously!]  
.small[\* this can fit in an existing Jetson Nano carrier boards]

???

V100 could rip through this data in a couple of mins, but consider the cost, power, etc.

Xavier NX is exciting, module that can slot into the Nano body [**hold up Nano device**]

---
class: middle

# Community engagement leading to empowerment

.pull.right[
<span style="color:#3498DB">... **a few stories of the journey** ...</span>
]

---

# So how about unlocking it for everyone?

.center[
<img src="images/JB_twitterprofile.png" style="width: 60%; margin-right: 1%; margin-top: 1em;"/>
]

---

# The unboxing and a slight snag

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/geforce2070_JB.png" style="width: 65%; margin-right: 1%; margin-top: 0em;"/>
  </div>
  <div class="fl w-50 bg-white tc">
    <img src="images/six_pin_plugs.png" style="width: 64%; margin-right: 63%; margin-top: 0em;"/>
  </div>
</article>

---

# Success

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/duct_tape.png" style="width: 65%; margin-right: 1%; margin-top: 0em;"/>
  </div>
  <div class="fl w-40 bg-white tc">
    <img src="images/nvidia_smi.png" style="width: 70%; margin-right: 1%; margin-top: 0em;"/>
  </div>
  <div class="fl w-40 bg-white tc">
    <img src="images/guppy_2070.png" style="width: 70%; margin-right: 1%; margin-top: 0em;"/>
  </div>
</article>

---
class: middle

# A global cast of many

* [***Kenya***] Jean-Bakka Domelevo Entfellner ([@JeanBakaDE](https://twitter.com/JeanBakaDE))

* [***USA***] John Erb-Downward ([@Bombanat](https://twitter.com/bombanat))

* [***Italy***] Luigi Faino ([@lfaino](https://twitter.com/lfaino))

* [***Switzerland***] Jürgen Hench

* [***USA***] Nvidia Clara Team ([Clara AGX site](https://developer.nvidia.com/clara-agx-devkit))

<br >

.center[You can follow the story here: [GitHub Gist - Xavier basecalling notes](https://gist.github.com/sirselim/2ebe2807112fae93809aa18f096dbb94)]

---

# ~~The future...~~

.center[
<img src="images/jetson_family.jpg" style="width: 45%; margin-right: 1%; margin-top: 0em;"/>
]

.center[
<img src="images/nvidia_tegra.jpg" style="width: 40%; margin-right: 1%; margin-top: 0em;"/>
]

---

# ~~The (not so distant) future...~~

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/xaviernx_seqkit.jpg" style="width: 97%; margin-right: 1%; margin-top: 0.5em;"/>
  </div>
  <div class="fl w-50 bg-white tc">
    <img src="images/xaviernx_compact_seqkit.jpg" style="width: 97%; margin-right: 1%; margin-top: 0.5em;"/>
  </div>
</article>

.center[
<img src="images/nvidia_tegra.jpg" style="width: 40%; margin-right: 1%; margin-top: 1.65em;"/>
]

---
class: hide_logo

# The present!

<article class="cf">
    <div class="fl w-100 w-33-m w-50-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/xavier-ont.gif);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
  <div class="fl w-50 w-33-m w-25-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/xavnx_board.jpg);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
  <div class="fl w-50 w-33-m w-25-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/xavnx_screen.jpg);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
  <div class="fl w-50 w-33-m w-25-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/Matt_hand.jpg);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
  <div class="fl w-50 w-33-m w-25-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/full_kit.jpg);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
</article>

---
class: hide_logo

# The present!

<article class="cf">
    <div class="fl w-100 w-33-m w-50-l pa1">
    <a class="db aspect-ratio aspect-ratio--1x1">
      <span role="img" style="background-image:url(images/IMG_20210203_102006.jpg);" class="bg-center cover aspect-ratio--object"></span>
    </a>
  </div>
  <div class="fl w-50 w-33-m w-25-l pa1">
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# The present!

Can you sequence SARS-Cov2 on ~$100 USD compute? ... **YES!**

.center[
<img src="images/nano_seq.jpg" style="width: 55%; margin-right: 1%; margin-top: 0em;"/>
]

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# Hot off the press!

.center[
<img src="images/adaptive_sampling.jpeg" style="width: 85%; margin-right: 1%; margin-top: 1.65em;"/>
<br />
&copy; Oxford Nanopore Technologies
]
.center[
<br />
Jürgen Hench, Basel, Switzerland ([cancer methylation sequencing](https://gist.github.com/sirselim/2ebe2807112fae93809aa18f096dbb94#gistcomment-3547889))
]

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# Hot off the press!

<article class="cf">
  <div class="fl w-50 bg-white tc">
    <img src="images/xavnx_phone.png" style="width: 45%; margin-right: 1%; margin-top: 0.5em;"/>
  </div>
  <div class="fl w-50 bg-white tc">
    <img src="images/minknowui.jpg" style="width: 97%; margin-right: 1%; margin-top: 0.5em;"/>
    <br>
    <br>
    <br>
    <br>
    <br>
    <b>Can now control all of this from our pockets!</b>  
    <br>
    <br>
    Available now on <a href="https://play.google.com/store/apps/details?id=com.nanoporetech.minknowui&hl=en_CA&gl=US" target="blank">Android</a> and <a href="https://apps.apple.com/us/app/minknow/id1504645283" target="blank">iOS</a>
  </div>
</article>

---

## Our experiences with the Jeston Xaviers

.small[
#### Article in the NZ Herald
  * The Genius of Genomics ([link](https://www.nzherald.co.nz/nz/the-genius-of-genomics-the-revolution-that-helped-nz-quash-covid-19/EFJWSHSL3TTYNNKYA5WEROIKHY/))
  * Story also on ESR website ([link](https://www.esr.cri.nz/home/about-esr/media-releases/esr-scientists-showcase-benefits-of-collaboration-for-rapid-dna-sequencing/))

#### Jetson Nanopore Sequencing 
  * [A place to collate notes and resources of our journey into porting nanopore sequencing over to accessible, portable technology](https://github.com/sirselim/jetson_nanopore_sequencing)
    * up to date information, including parts list and set up guide

#### eResearch 2020 presentation 
  * [Assessing the potential of ~~autonomous AI devices~~ cool tech for portable real-time sequencing](https://sirselim.github.io/presentations/eResearch_2020/eResearch_presentation_livedemo_2020#1)
    * live base-calling and presentation run from the Xavier

#### Xavier AGX setup and notes
  * [Xavier AGX unboxing and setup](https://hackmd.io/@Miles/HkumH7sBH)

#### Xavier base-calling benchmarking and notes
  * [Xavier benchmarking](https://gist.github.com/sirselim/2ebe2807112fae93809aa18f096dbb94#file-basecalling_notes-md)
]

---

# If you're interested in GPUs and genomics...

.center[
<img src="images/gpu_musing_tweet.png" style="width: 45%; margin-right: 1%; margin-top: 1.65em;"/>
<br />
[GPU musings (with an eye on genomics)](https://hackmd.io/@Miles/B1U-cOMyu)
]

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# Some parting thoughts

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# acknowledgements (people to 'nerd' out with!)

<div class="dt dt--fixed">
  <div class="dtc tc pv4 bg-white">
    <article class="mw5 center bg-white br3 pa3 pa4-ns mv3 ba b--black-10">
      <div class="tc">
        <img src="images/Matt_sm.png" class="br-100 h4 w4 dib ba b--black-05 pa2" title="Photo of team member">
        <h4 class="f3 mb2">Matt Storey</h4>
        <h4 class="f5 fw4 gray mt0">(ESR)</h4>
      </div>
    </article>
  </div>
  <div class="dtc tc pv4 bg-white">
    <article class="mw5 center bg-white br3 pa3 pa4-ns mv3 ba b--black-10">
      <div class="tc">
        <img src="images/Joep.jpg" class="br-100 h4 w4 dib ba b--black-05 pa2" title="Photo of team member">
        <h4 class="f3 mb2">Joep de Ligt</h4>
        <h4 class="f5 fw4 gray mt0">(ESR)</h4>
      </div>
    </article>
  </div>
  <div class="dtc tc pv4 bg-white">
    <article class="mw5 center bg-white br3 pa3 pa4-ns mv3 ba b--black-10">
      <div class="tc">
        <img src="images/Donia.png" class="br-100 h4 w4 dib ba b--black-05 pa2" title="Photo of team member">
        <h4 class="f3 mb2">Donia Macartney-Coxson</h4>
        <h4 class="f5 fw4 gray mt0">(ESR)</h4>
      </div>
    </article>
  </div>
</div>

.pull-left[.medium[
**Georgia Bell** (ESR)  
Una Ren (ESR)  
Richard Dean (ESR)
]]

.pull-right[.medium[
Matthew Walton (ESR)  
Shane Sturrock (ESR)  
Russell Smithies (ESR)  
]]

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