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<h1 class="mt-4 mb-3">NSF CAREER
<small>objectives, recruiting, questions</small>
</h1>
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<a href="index.html">Home</a>
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<li class="breadcrumb-item active">NSF CAREER</li>
</ol>
<div class="row job">
<div class="col-lg-12">
<h2>CiliaWeb: Integrated platform for foundational and reproducible ciliary beat pattern analysis</h2>
<h3>Overview</h3>
<p>
The overarching goal of this project is to develop a <strong>quantitative
and objective measure</strong> of ciliary motion beat patterns.
</p>
<div class="col-md-4" style="float:left;">
<img class="rounded-circle img-thumbnail" src="images/nsf-career/cilia_structure.png" alt="">
<caption class="figure-caption"><strong>Figure 1</strong>: Cell body and cilia as
viewed through a high-speed digital videomicroscope using
<a href="https://en.wikipedia.org/wiki/Differential_interference_contrast_microscopy">
differential interference contrast (DIC)</a> imaging.</caption>
</div>
<p>
<a href="https://en.wikipedia.org/wiki/Cilium">Cilia are microscopic
hair-like projections from cells</a> (Fig. 1). They beat in rhythmic patterns
and perform a variety of functions, such as mucociliary clearance
in the lungs and generating motility for sperm. Cilia also
play sensory and signaling roles that are largely understood
to involve the <em>primary</em> cilia, but which has also been
recently implicated in <em>motile</em> cilia. Cilia are present
along almost every major organ, including but not limited to:
lungs, brain, kidneys, and throat.
</p>
<p>
Because of their presence throughout nearly all the major organs
of the body, <a href="https://en.wikipedia.org/wiki/Ciliopathy">
ciliopathies, or diseases of the cilia</a>, can have wide-ranging
impacts. Nearly all ciliopathies are the result of genetic
mutations, but these mutations can impact either proteins that
form the ciliary <em>ultrastructure</em>, or the
<a href="https://en.wikipedia.org/wiki/Intraflagellar_transport">
intraflagellar transport (IFT)</a> system that kicks off
ciliogenesis, or the formation and maintainence system for
all the cilia in the body.
</p>
<div class="col-md-2" style="float: right;">
<img class="img-thumbnail" src="images/nsf-career/beat_patterns.png" alt="">
<caption class="figure-caption"><strong>Figure 2</strong>: Schematics of generally-
recognized phenotypes of ciliary motion.</caption>
</div>
<p>
Currently, the identification of ciliopathies is a process
involving multiple evaluation methods. One of the more well-known
methods is to compute <em>ciliary beat frequency</em> (CBF).
CBF outside of a "normal" range (10-12Hz) tends to indicate
the presence of a ciliopathy. However, there are numerous
confounding variables that can present as a CBF outside that
range despite the absence of a ciliopathy; conversely,
certain ciliopathies can present without a detectable change
in CBF. Finally, there is not a well-established methodology
for rigorously evaluating CBF for a given sample. Other
evaluation methods--electron microscopy to examine the ciliary
ultrastructure, evaluation of ciliary beat pattern--likewise
have utility but are ultimately not definitive.
</p>
<p>
In this project, it's the <strong>ciliary beat pattern</strong>
we are focused on. Researchers and clinicians generally recognize
the presence of multiple discrete ciliary beat patterns (Fig. 2), but
they are assessed entirely by manual inspection. Put another
way, there is no <strong>rigorously-defined library of ciliary
motion phenotypes</strong>.
</p>
<p>
We have established some methods that have proven useful
for large-scale quantitative screening and analysis of ciliary
motion. We first began investigating <a href="https://en.wikipedia.org/wiki/Optical_flow">
flow-based features</a> in our 2011 conference paper<sup>[<a href="#bsec">1</a>]</sup>. We
wrapped this into a full-fledged binary classifier in our
landmark 2015 <em>Science Translational Medicine</em>
publication<sup>[<a href="#stm">2</a>]</sup>, achieving over 90% classification accuracy of
normal versus abnormal ciliary motion using a support vector
machine trained on two different feature sets. These feature
sets revealed a low-dimensional manifold where the qualitative
differences between normal and abnormal ciliary motion could
be easily visualized (Fig. 3).
</p>
<div class="col-md-5" style="float:left;">
<img class="img-thumbnail" src="images/nsf-career/subspace.png" alt="">
<caption class="figure-caption"><strong>Figure 3</strong>: Normal (left) and
abnormal (right) ciliary motion, parameterized and
projected into a 3D principal component subspace.</caption>
</div>
<p>
This paper and its findings led to a multitide of additional
questions, many of which we are seeking to address as part
of this project.
</p>
<p>
<strong>What constitutes a "good" subspace of ciliary
motion, and how could it be used to identify ciliary
motion phenotypes?</strong> As indicated in Fig. 1, it's
well-established that multiple ciliary motion phenotypes
exist, but we have no way of quantitatively defining them.
Our 2015 paper "merely" performed normal/abnormal binary
classification, ignoring any other details. There is
evidence to suggest these "details" may correlate
with specific genetic mutations and, therefore, provide
a key for rapidly screening samples. On the advanced end,
being able to "generate" samples of ciliary motion that
adhere to certain motion statistics would be an incredibly
useful research and diagnostic tool.
</p>
<div class="col-md-5" style="float: right;">
<img class="img-thumbnail" src="images/nsf-career/segmentation.png" alt="">
<caption class="figure-caption"><strong>Figure 4</strong>: Cilia (left) and the
accompanying ground-truth segmentation mask (right) that
indicate regions containing cilia and not containing cilia.</caption>
</div>
<p>
<strong>How can cilia be automatically identified in video
samples?</strong> This may sound like a straightforward
application of <a href="https://en.wikipedia.org/wiki/Image_segmentation#Motion_&_Interactive_Segmentation">
semantic video segmentation</a> (we thought the same!), but it
turns out that for cilia this is a surprisingly difficult
challenge to do well<sup>[<a href="#isbi">3</a>]</sup> (Fig. 4).
Identifying cilia requires clever combinations of both spatial
and temporal features: cilia have a texture (sometimes),
and also motion (sometimes), but neither is definitive on its own.
Requiring researchers or clinicians to manually annotate
samples is not only extremely labor-intensive, it's also
very error-prone.
</p>
<p>
<strong>How can crowdsourcing be leveraged to include expert
input while still controlling for subjectivity?</strong> One
of the biggest drawbacks of the current process for ciliopathy
identification is that it relies heavily on manual inspection.
Nevertheless, the extensive clinical and/or laboratory training
that researchers undergo should not be discounted; rather, it
should be included while being kept in context.
<a href="https://en.wikipedia.org/wiki/Similarity_learning#Metric_learning">
Metric learning</a> provides a promising framework for how to
approach the inclusion of manual annotations into an automated
pattern recognition pipeline, but there is also physical
infrastructure that is required for this: how would the interface
be designed not only to encourage user recruitment and
retainment, but also to incentivize high-quality feedback?
</p>
<p>
<strong>How can researchers and clinicians be encouraged to
share their data and analyses?</strong> Notably, no open datasets
exist around cilia research, genomic or image. Furthermore, of
the little bit of software developed around ciliary motion or
structure analysis, none--including ours from the 2015 paper--
is available as open source. We aim to build an integrated
web platform, <em>CiliaWeb</em>, that is a one-stop-shop for
aggregating datasets (with permission, of course), building
reproducible ciliary analysis pipelines, and providing high-quality
interactive visualizations and feedback. We also aim to open source
the analytics and visualization engines developed as part of this
project, so researchers can deploy their own versions of CiliaWeb.
Finally, we're looking to generate a small amount of control
and experimental genomic and image data that can be openly and
publicly released for others to validate our results.
</p>
<h4>Any of this sound interesting? Read on!</h4>
<p>Citations
<small>
<ol>
<li><a name="bsec" href="http://dx.doi.org/10.1109/BSEC.2011.5872328">Novel Use of Differential Image Velocity Invariants to Categorize Ciliary Motion Defects</a></li>
<li><a name="stm" href="http://dx.doi.org/10.1126/scitranslmed.aaa1233">Automated identification of abnormal respiratory ciliary motion in nasal biopsies</a> </li>
<li><a name="isbi" href="https://arxiv.org/abs/1803.07534">Stacked Neural Networks for Automated Ciliary Motion Analysis</a></li>
</ol>
</small>
</p>
</div>
</div>
<div class="row job">
<div class="col-lg-12">
<a name="recruiting"></a>
<h3>Recruiting</h3>
<p>This project will always be recruiting! If you are interested in joining some aspect of the project, regardless of your experience level, <a href="mailto:squinn@cs.uga.edu?Subject=CiliaWeb">please contact me</a>!</p>
</div>
</div>
<br />
<div class="row job">
<div class="col-lg-12">
<h3>Frequently Asked Questions</h3>
<p>Some questions that have both been asked, or which I'm
hopefully cutting off at the pass.</p>
<p><strong>I'm interested in the project, but HOLY CRAP that list
of topics in the postdoc job ad is HUGE! Can I still apply?</strong></p>
<p style="padding-left: 20px;">YES! That list is meant to convey
the rich variety of topics spanned by this 5-year research
project, and to encourage people with a variety of backgrounds to
apply! Do you have highly theoretical machine learning expertise
in image representations? Apply! Are you an expert on web frameworks
and user interface design? Apply! Did you do some bench work and
computational analysis outside of imaging? Apply!</p>
<p><strong>I want to apply but my imposter syndrome is in full
swing and you'll probably get more qualified candidates than me.
Why should I apply?</strong></p>
<p style="padding-left: 20px;">Speaking as someone who at times
has been wholesale paralyzed by imposter syndrome, I can say
with confidence: you're more qualified than you think. Like any
person suffering from imposter syndrome, it's far more likely
that you'll be among the <em>most</em> qualified. So please apply!
Perhaps we could jointly plot ways to keep fooling everyone around us
while we do some really neat work studying cilia!</p>
<p><strong>Great! Here's my CV. When do I start getting paid?</strong></p>
<p style="padding-left: 20px;">This is a question I get a lot,
and unfortunately the answer usually isn't what people are hoping.
The bottom line is that I can't guarantee funding until we've
at least had a chance to speak in real-time. History (not just
mine) has demonstrated that while background and experience are
certainly important, far more important is how well you and I
(and <a href="people.html">the rest of my research group</a>)
can work together. That can only be assessed by setting up
some time to chat. Ideally this would entail taking a course with
me, though I know that's not always possible. Suffice to say,
we should set aside time to discuss things if you absolutely have
to be guaranteed funding before you'll even consider applying.</p>
<p style="padding-left: 20px;"><em>[NOTE: The above largely applies
only to doctoral student applicants. Postdoctoral candidates go
through a much more formal application and interview process.]</em></p>
<p><strong>I'm not really a team player; rather, I'm a wicked good
coder who will spend nights and weekends knocking down these research
questions. When can I start?</strong></p>
<p style="padding-left: 20px;">Never. The tech sector and academia
at large may still be enamored with the "difficult but talented"
individual, but that goes against our group ethos. Plus, "talent"
and "decency" are most assuredly <em>not</em> mutually exclusive! We
absolutely work hard, but we also explicitly focus on communication,
respect, and inclusiveness.</p>
<p><strong>Is this project only for doctoral students and postdocs?</strong></p>
<p style="padding-left: 20px;">Not at all! I've had quite a few
very successful undergraduate students conduct research with me for
course credit, for CURO, and even for transitioning into Double
Dawgs. Not only that, but I'm also an active participant in the
<a href="https://hr.uga.edu/employees/training/uga-young-dawgs-program/">
UGA Young Dawgs program</a> and recruited students from high
schools in the Athens area. My only preference for recruiting
undergraduates is that you start working with me in your second
or third year, so we have time to develop some momentum and
develop a good professional rapport.</p>
<p style="padding-left: 20px;">If you're an undergraduate and
want to work on this project, just
<a href="mailto:squinn@cs.uga.edu?Subject=Interested in CiliaWeb">
shoot me an email</a>!</p>
<p><strong>I'm a life sciences student/graduate with little to no
computational experience. Should I still apply?</strong></p>
<p style="padding-left: 20px;">As long as you are open to and
enthusiastic about picking up at least some computational skills,
then absolutely yes! You will be expected to pick up
some fundamental skills in machine learning and coding, and this will
certainly comprise the majority of your work, but there will also
be opportunities to do some bench and wet lab work.</p>
<p><strong>I have a question that isn't answered here. How do I
get it answered?</strong></p>
<p style="padding-left: 20px;"><a href="mailto:squinn@cs.uga.edu?Subject=CiliaWeb FAQ">Email me!</a></p>
</div>
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<h3>Award Details</h3>
<p>
<table class="table-striped table-condensed table-bordered" width="75%">
<tr>
<th>Abstract</th>
<td><a href="https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845915">#1845915</a></td>
</tr>
<tr>
<th>NSF Directorate</th>
<td><a href="https://www.nsf.gov/dir/index.jsp?org=BIO">Biological Sciences (BIO)</a></td>
</tr>
<tr>
<th>NSF Division</th>
<td><a href="http://www.nsf.gov/div/index.jsp?div=DBI">Biological Infrastructure (DBI)</a></td>
</tr>
</table>
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