+[[!meta title="Archives"]]
[[!if test="archives/*" then="""
Browse through blog archives by year:
[[!map pages="./archives/* and !./archives/*/* and !*/Discussion"]]
+[[!meta description="Don Armstrong's blog and web pages. Don Armstrong is a Bioinformatician and Debian Developer currently a postdoc at the University of Southern California and living in Riverside, CA."]]
+
+[[!inline pages="./posts/* and !*/Discussion" show="10"
+actions=yes rootpage="posts"]]
+
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[[!sidebar]]
""" else="""
[[!inline pages=sidebar raw=yes]]
"""]]
-[[!inline pages="./posts/* and !*/Discussion" show="10"
-actions=yes rootpage="posts"]]
-
This blog is powered by [ikiwiki](http://ikiwiki.info).
* local.css and use it to override or change settings in this one.
*/
+@import url("/fonts/liberationserif/stylesheet.css");
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+.sidebar p {
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--- /dev/null
+[[!meta title="Dropbox Recursive Downloader"]]
+
+I'm working on some analyses for the
+[Genetic Analysis Workshop #19](http://www.gaworkshop.org/gaw19/index.html),
+which has placed it's data on Dropbox. Unfortunately, Dropbox doesn't
+allow for people to download zip archives larger than 1GB, and the
+data was made available in an unpacked structure with more than a
+hundred files. Some searching indicated that no one had written a
+recursive downloader for Dropbox, so 30 minutes of hacking with
+[WWW::Mechanize](http://search.cpan.org/~ether/WWW-Mechanize-1.73/lib/WWW/Mechanize.pm)
+later, I wrote a
+[simple recursive downloader for Dropbox](http://git.donarmstrong.com/?p=bin.git;a=blob;f=dropbox_recursive;hb=HEAD).
+
+Two hours later, all of the files had downloaded.
+
+[[!tag tech debian genetics]]
--- /dev/null
+[[!meta title="Plotting Embedded Bitmap in Vector Plot in R"]]
+
+Recently, one of my collaborators complained that one of my plots took
+forever to render on his machine. The particular plot in question had
+a few thousand points, many of which were overlapping. Ideally, R
+would be able to simplify the vector image which was drawn to avoid
+drawing points which were occluded by other points, but this is
+difficult to do properly, and R currently doesn't do it.
+
+However, R is able to plot to a bitmap, and bitmap images have the
+nice property of automatically handling this for you. Furthermore,
+raster images have recently been made far less clunky in R, so it's
+pretty easy to shove an arbitrary bitmap image anywhere. With
+`dev.capture` in Cairo coupled with `grid.raster` in grid, we have
+everything we need to solve this problem:
+
+[[!format R """
+require(grid)
+require(Cairo)
+
+start.rasterplot <- function(width=NULL,height=NULL) {
+ x.y.ratio <- convertX(unit(1,"npc"),"mm",valueOnly=TRUE)/
+ convertY(unit(1,"npc"),"mm",valueOnly=TRUE)
+ width.points <- as.numeric(convertX(unit(1,"npc"),"points"))
+ dpi <- as.numeric(convertX(unit(1,"inch"),"point"))
+ if (is.null(width) && is.null(height)) {
+ width <- 1024
+ }
+ if (is.null(width)) {
+ width <- height*x.y.ratio
+ }
+ if (is.null(height)) {
+ height <- width/x.y.ratio
+ }
+ Cairo(width=width,height=height,dpi=1024/width.points*dpi,file="/dev/null")
+}
+
+stop.rasterplot <- function(plot=TRUE) {
+ raster.image <- dev.capture(native=TRUE)
+ dev.off()
+ if (plot) {
+ grid.raster(raster.image,width=unit(1,"npc"),height=unit(1,"npc"))
+ return(invisible())
+ } else {
+ return(raster.image)
+ }
+}
+"""]]
+
+Now we can do the following:
+
+[[!format R """
+pdf(file="raster.pdf")
+start.rasterplot()
+print(xyplot(y~x,
+ data=data.frame(y=rnorm(1E8),x=rnorm(1E8))))
+stop.rasterplot()
+dev.off()
+"""]]
+
+and our PDF will contain a raster image, and will load in seconds
+instead of taking forever to plot the file.
+
+[[!tag r genetics biology]]
--- /dev/null
+[[!meta title="ErgoDox keyboard assembly"]]
+
+[[!agimg don_lab/017_even_more_lab_desk_10232003.jpg]]
+
+I routinely use a Kinesis Advantage Pro keyboard, which is a split,
+ergonomic keyboard with thumb clusters that uses brown cherryMX
+switches. Over the thirteen years that I've been using it, I've become
+a huge fan of this style of keyboard. However, I have two major
+annoyances with the Kinesis. First, while the firmware is good,
+remapping the keys is complicated and producing more complicated
+keyboard layouts with layers and keycodes that are not present in the
+original layout is not possible. Secondly, the interconnect between
+the main key wells and the controller board in the middle occasionally
+fails, and requires disassembly and occasional re-tinning of the
+circuit board interconnect connector.
+
+[[!agimg 2014/08_August/20140801_ergodox/IMG_20140801_232557.jpg]]
+1
+About a year ago, I became aware of the [ErgoDox](http://ergodox.org/)
+keyboard, which is a keyboard design which mimics the kinesis to some
+degree, but with completely separated key halves (useful, because I'm
+substantially bigger than the average human), programmable firmware
+(so I can finally have the layers and missing keys) and with slightly
+more elegant interconnects (TRRS cables). Unfortunately, at the time I
+first heard about it (and other custom keyboards), making it required
+sourcing circuit boards, parts, and finding someone to cut a case for
+the keyboard. Then, a few months ago, I learned about
+[MassDrop](http://www.massdrop.com), a company who puts together
+groups of people to do buys of products at near-wholesale level
+prices, and their offer of all of the parts to
+[build an ErgoDox](https://www.massdrop.com/buy/ergodox). After
+waiting for a group buy of the keyboard to become available, I put in
+an order, and received the parts two months later.
+
+Over a few hours yesterday, I learned how to do surface mount
+soldering of the 78 diodes (one for each key), and finished assembling
+and flashing the firmware. This morning, I fixed up the few key
+bindings that I needed to be productive, and viola, my laptop at home
+now has a brand new ergonomic keyboard.
+
+
+[[!tag tech debian keyboards]]
--- /dev/null
+[[!meta title="Debian Booth at Scale 12x"]]
+
+I spent the weekend at
+[SCALE 12x](http://www.socallinuxexpo.org/blog/scale-12x) running the
+[Debian](http://www.debian.org) booth. SCALE is one of the best
+conferences that I get to attend every year; it has a great mix of
+commercial exhibitors and community groups, and routinely gets great
+speakers. As I've done for quite some time, I organized a Debian booth
+there, and talked to lots of people about Debian.
+
+[[!agimg "2014/02_February/scale_12x_debian_booth.jpg"]]
+
+If you're in the Southern California area, or have a chance to give a
+talk for SCALE 13x, you should do so! Thanks again to Matt Kraai and
+Paul Hardy for helping out in the Debian booth all weekend!
+
+[[!tag debian scale tech]]
+
if [ "x$1" == "xdoit" ]; then
if git status --porcelain -z | grep -z '^ M' | grep -zq $ORG_GREP; then
- git status --porcelain -z | grep -z '^ M' | grep -z $ORG_GREP | \
- sed -z 's/^ M//g' | \
+ git status --porcelain -z | grep -z '^ M' | grep -z $ORG_GREP | \
+ sed -z 's/^ M//g' | \
xargs -0 git commit -m'update org files'
git push;
fi;
-Projects
-========
+[[!meta title="Projects"]]
- These are some of the more recent publicly available projects that
- I've been working on. Most of the code here is available under the
- GPL, but check the licences in individual files or e-mail me if it is
- unclear. Everything here is primarily used by me, and may not be
- suitable for you. Feel free to e-mail me with any questions or
- patches, though. As always, Caveat Lector.
+Here are some of the many projects I'm working on or have previously
+worked on.
+[[!toc levels=2]]
+Debian
+======
-Reference System
-----------------
+I use [Debian](http://www.debian.org) on all of my computers and
+regularly contribute to it. You can see some of the work I'm doing in
+Debian below.
-Originally written in PHP, the reference system is being totally
-rewritten in perl with mod_perl, postgresql and various other
-routines. It was originally designed to track scholarly articles and
-hold note and references related to them. However, the new version of
-the system will be used to track everything from books to images to
-newspapers to songs. Basically, it's a portable memory system that
-happens to be web based and accessible from any where in the planet.
+* [My Debian packages](http://qa.debian.org/developer.php?login=don)
+* [Debbugs](http://wiki.debian.org/Teams/Debbugs) -- the bug tracking
+ system for Debian
+* [Listmaster](http://wiki.debian.org/Teams/Listmaster) -- mailing
+ list maintainers for [lists.debian.org](http://lists.debian.org)
+* [Technical Committee](http://www.debian.org/devel/ctte) -- Debian's
+ technical decision making board; responsible for resolving technical
+ disputes between developers
- * [PHP CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/ref_php/?root=Ref+CVS)
- * [New CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/ref/?root=Ref+CVS)
-Utilities Modules
------------------
-The new reference system has lead me to redesign many of the modules
-that I use alot. Most of them now can be plugged into and out of perl
-programs at will, decreasing development time of mod_perl based web
-projects. More importantly, it makes my code a lot more modular, and
-keeps me from going insane tracking it all.
-
- * Class::Modular is a superclass that allows one to generate a single
- class from modules spread throughout multiple files and overload
- methods within that class at will. Da::DB inherits from
- Class::Modular. [svn repository](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/?root=Class+Modular)
- * Da::DB is the main Database class. All (or almost all) database
- interaction occurs through da_dbh objects or dynamically loaded sub
- modules of Da::DB. (The new Template::Provider code is an example
- of a loadable sub module.) [svn repository](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/?root=Da+DB)
+Debbugs
+-------
-Micro Array Utilities
----------------------
-These R functions and a few perl scripts are used to analyse Gene
-Microarray data from affymetrix datafiles.
+Debbugs is Debian's Bug Tracking System. I am currently the primary
+maintainer of debbugs. You can see what I'm working on in
+[my git repositories](http://git.donarmstrong.com/debbugs.git), what I
+need to work on in
+[Debbug's bug list](https://bugs.debian.org/debbugs),
+[read more information](http://wiki.debian.org/Teams/Debbugs) about
+contributing to Debbugs yourself, and see all of
+[my posts](/tags/debbugs/) about Debbugs.
- * [CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/ma_utilities/?root=RZ+Lab+CVS)
- * [Download](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/ma_utilities/ma_utilities.tar.gz?tarball=1&root=RZ+Lab+CVS)
-LaTeX Math to PNG
+Debian R Packages
-----------------
-Converts LaTeX math formula to PNG files. ($$x^2_0+y^2_0=r^2_0$$)
-becomes 
- * [CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/?root=RZ+Lab+CVS)
- * [Source](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/latexmath2png.pl?rev=HEAD&root=RZ+Lab+CVS&content-type=text/vnd.viewcvs-markup)
- * [Download](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/latexmath2png.tar.gz?tarball=1&root=RZ+Lab+CVS)
+I maintain
+[builds of the vast majority of R packages for Debian](/r/debian_r).
+You can also see [my posts](/tags/debian-r) about the Debian-r archive.
+
+Bioinformatics
+==============
+
+Below are some of the bioinformatics and biologically relevant tools I
+have built.
-Diary Script
---------------------
+Postgresql Mirror of dbSNP
+--------------------------
+
+Being able to query [dbSNP](http://www.ncbi.nlm.nih.gov/SNP/) locally
+is very useful for adding annotations to deep sequencing results and
+other DNA polymorphism based analyses. See how to set up a
+[postgresql mirror of dbsnp](/genetics/dbsnp_mirror/) yourself using
+my scripts.
- * [Source](diary/diary.html)
- * [Download](diary/diary.gz)
-
Helical Wheel Plots
-------------------
Plots alpha helical wheels with hydrophobic moment according to the
* [Download](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/wheel/wheel.tar.gz?tarball=1&root=RZ+Lab+CVS)
* [CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/wheel/?root=RZ+Lab+CVS)
-Frog's Leap Website
--------------------
-Various Scripts and HTML design for both the flash and html sections of the site using perl and javascript.
-* [Link](http://www.frogsleap.com)
+Ikiwiki Plugins
+===============
+
+My entire website is now built using [ikiwiki](http://ikiwiki.info).
+Here are some ikiwiki plugins I have written:
+
+* [Sweavealike](http://git.donarmstrong.com/?p=ikiwiki_plugins.git;a=blob;f=sweavealike.pm;hb=HEAD)
+ is a plugin for [IkiWiki](http://ikiwiki.info) that tries to do some
+ of the useful things for IkiWiki that Sweave/Knitr does for R and
+ LaTeX. See [my blog post](/posts/introducingsweavealike) for more
+ information.
+
+
+Perl Modules
+============
+
+* Class::Modular is a superclass that allows one to generate a single
+ class from modules spread throughout multiple files and overload
+ methods within that class at will. Da::DB inherits from
+ Class::Modular.
+ [svn repository](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/?root=Class+Modular)
+
+
+LaTeX Math to PNG
+-----------------
+Converts LaTeX math formula to PNG files. ($$x^2_0+y^2_0=r^2_0$$)
+becomes 
+
+ * [CVS](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/?root=RZ+Lab+CVS)
+ * [Source](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/latexmath2png.pl?rev=HEAD&root=RZ+Lab+CVS&content-type=text/vnd.viewcvs-markup)
+ * [Download](http://rzlab.ucr.edu/cgi-bin/viewcvs.cgi/latexmath2png/latexmath2png.tar.gz?tarball=1&root=RZ+Lab+CVS)
-Resume
-======
+[[!meta title="Curriculum Vitæ, Research Statement, and Teaching Statement"]]
-[Don Armstrong](http://www.donarmstrong.com/)
+Introduction
+------------
+A brief statement of my research interests and teaching mission
+follows, and my [Curriculum Vitæ](curriculum_vitae)
+([pdf](dla-cv.pdf)),
+[Research Statement](research_statement)
+([pdf](research_statement.pdf)), and
+[Teaching Statement](teaching_statement)
+([pdf](teaching_statement.pdf)) are also available.
+
+For my contact information or additional references, please e-mail
<don@donarmstrong.com>
-<http://www.donarmstrong.com>
-
-[Phone contact information available via e-mail.]
-
-I am a practitioner of the art of solving problems as elegantly and
-practically as possible. I seek to enhance my abilities to solve
-problems in the digital realm by learning (and inventing where
-appropriate) new methods and techniques, and to help others achieve
-their goals by removing or smoothing over ponderous obstacles in their
-path. If you have difficult problems for which a digital approach
-seems appropriate, I'm the person to talk to to find a solution.
-
-Education
-----------
-* Doctor of Philosophy in Cell, Molecular and Developmental Biology from [UC Riverside](http://www.ucr.edu), 2008
-* Bachelor of Science in [Biology](http://bio.ucr.edu) from [UC Riverside](http://www.ucr.edu), 2001
-* Graduate, Scholar with Distinction from [Marina High School](http://www.hbuhsd.k12.ca.us/mhs/), 1997
-
-Experience
-----------
-* July 2002-July 2003: Researcher for Socratech, LLC
- * Affymetrix Gene Microarray Analysis using R, and Perl.
- * Custom designed cell, tissue and data tracking system in perl
- * Analysis of MA results using Gene Ontology
- * Literature minining using custom designed Perl scripts to search pubmed.
-* Jun. 2000-Jun 2001: Computer Resource Coordinator for [UC Riverside](http://www.ucr.edu)
- * Network administration/design of a 2000+ node network
- * developed web based registration system using bash, dhcp, perl, php and mysql
- * Developed network monitoring system
- ([rnm](http://rnm.sourceforge.net)) using php, mysql, perl, and
- snmp.
- * Supervised a staff of 13 RCCs<LI>Administration of 7+ Unix Servers (Apache,ISC DHCP, MySQL, mod_perl, slash)
- <LI>Computer Lab Administration (NT)
- <LI>Developed a printer recharge/tracking system using card readers, perl, mysql, and lpr-ng
- <LI>Developed a customer-tech Help Request System/Billing System using php, mysql, smtp, and perl
-
-Skills
-------
-
-
-Projects
---------
-[Current projects|projects]
-
-References
-----------
-Available Upon Request.
+Research Focus
+--------------
+
+My primary research focus is developing and using bioinformatics
+techniques to identify causes and mechanisms underlying human
+diseases, such as Systemic Lupus Erythematosus (SLE). I have
+identified multiple novel genes associated with SLE using both
+genome-wide association studies and trio-based studies in targeted
+regions. In collaborative work, I have identified a causal variant in
+NCF2
+([rs17849502](http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=rs17849502))
+using both *in silico* and *in vitro* approaches. I am currently
+working on identifying causal variants in additional associated genes
+using targeted deep sequencing using high-throughput variant analysis
+pipelines to prioritize variants for additional *in silico* and *in
+vitro* experiments. In the future, utilizing my extensive
+bioinformatic and software development experience, I will head a
+development group working on techniques for the storage, alignment,
+and analysis of terabytes (eventually petabytes) of next-generation
+sequencing data from collaborations studying human-relevant diseases
+and biological systems.
+
+
+Teaching Mission
+----------------
+
+While teaching, my primary mission is to have my students experience
+the excitement of scientific discovery for themselves. Secondarily, I
+use that excitement to keep them engaged and interested in the
+material. While a graduate student at UC Riverside, I was a teaching
+assistant for [Introductory Biology, Genetics, Molecular Biology, and
+Developmental Biology](http://www.biology.ucr.edu/courses/UGcourses.html)
+
--- /dev/null
+[[!meta title="Curriculum Vitæ"]]
+Curriculum Vitæ
+===============
+
+* [Don Armstrong](http://www.donarmstrong.com/)
+* <don@donarmstrong.com>
+* <http://www.donarmstrong.com>
+
+Education
+----------
+* Doctor of Philosophy
+ * 2001-2008 **Cell, Molecular and Developmental Biology**.
+ [University of California at Riverside](http://www.ucr.edu).
+ Dissertation: The Role of membrane Composition in the Activity of
+ Membrane-Associated Signal Transduction Proteins.
+* Bachelor of Science
+ * 1997-2001 [Biology](http://bio.ucr.edu).
+ [University of California at Riverside](http://www.ucr.edu).
+
+Postdoctoral Experience
+-------------------------
+
+### University of Southern California ###
+
+* 2013--Present. Postdoctoral researcher under Chaim O. Jacob.
+ Identifying genes and causal alleles associated with Systemic Lupus
+ Erythematosus using genome-wide association, next-generation
+ sequencing, computational and biochemical approaches.
+* 2009--2010. Postdoctoral researcher under Florence M. Hofman.
+ Identifying signaling pathways which are responsible for the
+ functional alteration of endothelial cells in glioblastoma
+ multiforme and arteriovenous malformations.
+
+### University of California at Riverside ###
+* 2010--2012. Postdoctoral researcher under Raphael Zidovetzki.
+ Identifying genes which are associated with Systemic Lupus
+ Erythematosus using prior information and targeted trio-based
+ studies.
+
+Teaching
+--------
+### Teaching Assistant ###
+* 2004--2007. University of California at Riverside. First and second
+ quarter introduction to biology for majors (BIO 5A and 5B).
+ Introduction to Genetics (BIO 102), Human Embryology (CBNS 169).
+
+Work in Industry
+----------------
+### Non-Profit ###
+* 2004--Present. [Debian Project](http://www.debian.org), Developer;
+ Technical Committee Member (2010--Present)
+
+### Employment Experience ###
+* 2002-2003. **Socratech** in Rochester, NY. Bioinformatics researcher:
+ developed new microarray analysis methods for a start-up
+ biotechnology company working on developing treatments for
+ Alzheimer's disease
+
+Publications
+------------
+## Refereed Publications ##
+1. **Don L. Armstrong**, Raphael Zidovetzki, and Chaim O Jacob. Novel
+ lupus associated genes discovered in GWAS; two signals explain all
+ HLA SNPs in European Americans. *Genes Immun*, In press.
+
+2. Chaim O Jacob, Miriam Eisenstein, Mary C Dinauer, Wenyu Ming,
+ Qiang Liu, Sutha John, Francesco P Quismorio, Andreas Reiff, Barry
+ L Myones, Kenneth M Kaufman, Deborah McCurdy, John B Harley, Earl
+ Silverman, Robert P Kimberly, Timothy J Vyse, Patrick M Gaffney,
+ Kathy L Moser, Marisa Klein-Gitelman, Linda Wagner-Weiner, Carl D
+ Langefeld, **Don L Armstrong**, and Raphael Zidovetzki.
+ Lupus-associated causal mutation in neutrophil cytosolic factor 2
+ (NCF2) brings unique insights to the structure and function of
+ NADPH oxidase. *Proc Natl Acad Sci USA*, 109(2):59--67, Jan 2012.
+3. **Don L Armstrong**, Omer Markovitch, Raphael Zidovetzki, and Doron
+ Lancet. Replication of simulated prebiotic amphiphile vesicles
+ controlled by experimental lipid physicochemical properties. *Phys
+ Biol*, 8(6):066001, Dec 2011.
+
+4. Christopher J Stapleton, **Don L Armstrong**, Raphael Zidovetzki,
+ Charles Y Liu, Steven L Giannotta, and Florence M Hofman.
+ Thrombospondin-1 modulates the angiogenic phenotype of human
+ cerebral arteriovenous malformation endothelial cells.
+ *Neurosurgery*, 68(5):1342--53, May 2011.
+
+5. **D L Armstrong**, A Reiff, B L Myones, F P Quismorio, M
+ Klein-Gitelman, D McCurdy, L Wagner-Weiner, E Silverman, J O
+ Ojwang, K M Kaufman, J A Kelly, J T Merrill, J B Harley, S-C Bae, T
+ J Vyse, G S Gilkeson, P M Gaffney, K L Moser, C Putterman, J C
+ Edberg, E E Brown, J Ziegler, C D Langefeld, R Zidovetzki, and C O
+ Jacob. Identification of new SLE-associated genes with a two-step
+ Bayesian study design. *Genes Immun*, 10(5):446--56, Jul 2009.
+
+6. Chaim O Jacob, Jiankun Zhu, **Don L Armstrong**, *et al.*
+ Identification of IRAK1 as a risk gene with critical role in the
+ pathogenesis of systemic lupus erythematosus. *Proc Natl Acad Sci
+ USA*, 106(15):6256--61, Apr 2009.
+
+7. Bahram Namjou, Andrea L Sestak, **Don L Armstrong**, Raphael
+ Zidovetzki, *et al.* High-density genotyping of STAT4 reveals
+ multiple haplotypic associations with systemic lupus erythematosus
+ in different racial groups. *Arthritis Rheum*, 60(4):1085--95, Apr 2009.
+
+8. **Don Armstrong** and Raphael Zidovetzki. Amplification of
+ diacylglycerol activation of protein kinase c by cholesterol.
+ *Biophys J*, 94(12):4700--10, Jun 2008.
+
+9. **Don L Armstrong**, Chaim O Jacob, and Raphael Zidovetzki.
+ Function2gene: a gene selection tool to increase the power of
+ genetic association studies by utilizing public databases and
+ expert knowledge. **BMC Bioinformatics**, 9:311, 2008.
+
+10. Chaim O Jacob, Andreas Reiff, **Don L Armstrong**, Barry L Myones,
+ Earl Silverman, Marisa Klein-Gitelman, Deborah McCurdy, Linda
+ Wagner-Weiner, James J Nocton, Aaron Solomon, and Raphael
+ Zidovetzki. Identification of novel susceptibility genes in
+ childhood-onset systemic lupus erythematosus using a uniquely
+ designed candidate gene pathway platform. *Arthritis Rheum*,
+ 56(12):4164--73, Dec 2007.
+
+11. Raphael Zidovetzki, Burkhard Rost, *Don L Armstrong*, and Israel
+ Pecht. Transmembrane domains in the functions of fc receptors.
+ *Biophys Chem*, 100(1-3):555--75, 2003.
+
+12. **Don L Armstrong**, Dan B Borchardt, and Raphael Zidovetzki.
+ Synergistic perturbation of phosphatidylcholine/sphingomyelin
+ bilayers by diacylglycerol and cholesterol. *Biochem Biophys Res
+ Commun*, 296(4):806--12, Aug 2002.
+
+13. Zhenhua Wu, Huang Guo, Nienwen Chow, Jan Sallstrom, Robert D Bell, Rashid
+ Deane, Andrew I Brooks, Suhasini Kanagala, Anna Rubio, Abhay Sagare, Dong
+ Liu, Fang Li, **Don Armstrong**, Thomas Gasiewicz, Raphael Zidovetzki, Xiaomei
+ Song, Florence Hofman, and Berislav V Zlokovic. Role of the meox2 homeobox gene in neurovascular dysfunction in
+ alzheimer disease. *Nat Med*, 11(9):959--65, Sep 2005.
+
+14. Rashid Deane, Shi Du Yan, Ram Kumar Submamaryan, Barbara LaRue,
+ Suzana Jovanovic, Elizabeth Hogg, Deborah Welch, Lawrence Manness,
+ Chang Lin, Jin Yu, Hong Zhu, Jorge Ghiso, Blas Frangione, Alan
+ Stern, Ann Marie Schmidt, **Don L Armstrong**, Bernd Arnold,
+ Birgit Liliensiek, Peter Nawroth, Florence Hofman, Mark Kindy,
+ David Stern, and Berislav Zlokovic. Rage mediates amyloid-beta peptide transport across the blood-brain
+ barrier and accumulation in brain. *Nat Med*, 9(7):907--13, Jul 2003.
+
+Selected Presentations
+----------------------
+### Conference Presentations ###
+* 2007-06-07. FOCIS 2007. Uniquely designed candidate gene
+ identification platform discovers novel genes in childhood-onset
+ SLE.
+
+References
+----------
+Please e-mail <don@donarmstrong.com> for references
+
--- /dev/null
+
+
+# Research Objectives
+
+## Uncovering genetic causes of diseases using a multidisciplinary bioinformatics-driven approach
+
+
+
+My research focuses on designing and using bioinformatics techniques
+to identify causes and mechanisms underlying human diseases such as
+Systemic Lupus Erythematosus, Glioblastoma Multiforme, and
+Arteriovenous Malformations followed be designing appropriate
+diagnostics and treatment methods. Once identified, I work with
+collaborators to verify the bioinformatics-discovered mechanisms
+utilizing *in silico*, *in vitro*, and *in vivo* techniques, and
+develop therapeutic and diagnostic techniques to identify and treat
+the underlying human disorder. Cell-culture-based methods are utilized
+as the first step in designing multi-target treatments, followed by
+appropriate animal models..
+
+# Unique Qualifications
+
+## Straddling Biology, Computer Science, and Statistics
+
+In addition to being a cellular and molecular biologist, I have
+extensive experience in algorithm design, computer programming, and
+statistics. The combination of these areas enables me to handle
+biological problems which involve large numbers of samples and data
+and require statistical analysis which can address confounders which
+are often present in non-laboratory settings. It also gives me a
+unique perspective which enables me to design novel methods to analyze
+and interpret large amounts of data.
+
+## Multidisciplinary approach
+
+I have published in multiple disciplines, including membrane
+biophysics, bioinformatics, genetics, and cellular biology. My
+experiences in these fields and my experiences while transitioning
+fields has allowed me to apply unique insights garnered from my
+previous work to new topics leading to novel approaches and
+breakthrough discoveries.
+
+# Previous Research Projects
+
+
+
+## Genetic Basis of System Lupus Erythematosus (SLE)
+
+I developed novel bioinformatic methods which increase
+
+
+likelihood of identifying reproducible genetic associations using
+prior knowledge from publicly available databases and expert
+information [^Armstrong2008:function2gene]. Using these methods, I was
+able to identify genes previously unassociated with SLE in a
+trio-based study [^Jacob2007:ar_lupus]. These genes were then
+replicated in a larger case-control study which was funded by the NIH
+on the basis of the original findings [^Jacob2009:sle_irak1],[^Armstrong2009:sle_gi].
+Among other findings, this larger study
+identified a missense allele in NCF2 (H389Q, rs17849502) which was
+associated with SLE. Collaborative work indicated that H389Q altered
+the binding energy of NCF2 with VAV1 using docking simulations, and in
+vitro experiments confirmed that H389Q altered NADPH oxidase function
+[^Jacob2012:sle_ncf2], thus identifying it as a causative SLE
+mutation.
+
+## Cancer Stem Cells in Glioblastoma
+
+Glioblastoma is a almost invariably fatal form of brain cancer[^survival_rate] which is
+diagnosed in \(\approx\) 9,000 people in the US annually. It is typified
+by high levels of chemotherapeutic-resistant recurrences, some of
+which is likely caused by cancer stem cells which are insensitive to
+many chemotherapeutic agents. In collaboration with Florence Hoffman
+at USC, I have classified glioblastoma-derived cancer stem cells and
+cancer cell lines into distinct classes using gene microarrays and
+various clustering approaches, which will enable the design of a
+class-specific treatment of this devastating disease.
+
+## Regulatory pathways underlying cranial arteriovenous malformations
+
+The mechanisms underlying the formation of arteriovenous
+malformations[^avm_definition] (AVMs) which occur in the brain are
+unknown. Using gene microarrays, qtPCR, and *in vitro* experiments on
+primary human endothelial cells cultured from resected AVMs, I
+indentified multiple gene regulation pathways, many of them novel,
+including the Id1/Thsb1 inhibitory pathway. Additional experiments
+indicated that the *in vitro* pathology of endothelial cells could be
+partially rescued using extracellular Thsb1
+[^Stapleton2011:thbs1].
+
+# Future research directions
+
+## Identification of causal mutations in SLE
+
+While many regions and SNPs which are associated with SLE have been
+identified, few of those regions have identified causal alleles with
+known function. Furthermore, even for regions with identified causal
+alleles, no systematic searches have been performed to identify
+additional causal regions. Continuing my existing collaboration with
+Chaim O. Jacob, I will rectify this by
+
+1. Deep sequencing the associated regions in 500 lupus cases and 1000 controls
+
+2. Identifying which newly found variants are associated with SLE
+
+3. Selecting variants with a high likelihood of producing functional variants
+
+4. Verifying biological relevance of variants by *in vitro* study
+
+5. Verifying functional relevance in human subjects
+
+## Developing analysis tools for massive amounts of sequencing data
+
+The ability to cheaply and rapidly sequence large numbers of samples
+has massively increased the amount of data processing required by
+researchers. Compounding this increase in data, most existing tools
+have not been designed to take full advantage of the current advances
+in computer architecture, which parallel solutions to problems which
+can be run on architectures with vastly differing computational
+abilities (such as GPUs).
+
+To resolve this, I am in the process of actively developing new open
+source tools[^extending_note] which are capable of running on
+massively parallel architectures using both multiple computers
+(openMPI) and multiple GPUs on the same computer (Nvidia's CUDA) to
+
+1. Develop an open source massively parallel imputation method which
+ can combine existing GWAS results with new deep sequencing
+ and genetic profiling results.
+
+2. Extend same tools to call SNPs both incrementally and in parallel.
+
+I am currently working on extending samtools (an Open Source SNP
+calling suite) to support running on multiple computers.
+
+## Gut microbiota alteration in SLE
+
+Many autoimmune disorders are known to be affected by gut microbiota.
+Preliminary evidence suggests that mice which develop SLE have
+differences in gut microbiota from mice which do not develop SLE,
+which suggests that SLE severity may also be affected by differences
+in human gut microbiota. I am currently developing novel methods to
+
+1. Determine which gut microbiota differ between mice with and
+ without SLE and using 16S sequencing
+
+2. Determine which gut microbiota differ between humans with and
+ without SLE using 16S sequencing, given #1.
+
+## Continuous, incremental analysis
+
+Just as science requires continuous testing of hypotheses,
+bioinformatics is slowly moving towards continuous incremental
+analysis of data. Most current tools use iterative analysis, where
+analyses must be completely re-run with each new piece of data that is
+obtained. When the amount of data remains small relative to the
+overall computing power available, this is a feasible approach.
+However, as the amount of data increases, it stops being feasible to
+completely reanalyze data as new data is obtained, and incremental
+analysis approaches are necessary. I will be working to extend
+existing analysis pipelines to handle the incremental analysis of
+data.
+
+# Research Funding
+
+## Funding Opportunities
+
+I anticipate obtaining funding from the following sources to pursue
+the research goals outlined previously:
+
+1. National Institute of Health
+
+ 1. [Research Project Grant (RO1)](http://grants.nih.gov/grants/guide/pa-files/PA-13-302.html) (NHGRI, NIAID, BISTI)
+
+ 2. [NLM Career Development Award in Biomedical Informatics (K01)](http://grants.nih.gov/grants/guide/pa-files/PAR-13-284.html)
+
+ 3. [Continued Development and Maintenance of Software (R01)](http://grants.nih.gov/grants/guide/pa-files/PAR-11-028.html) (extending existing biofinformatics software)
+
+2. Alliance for Lupus Research
+
+ 1. [Target Identification in Lupus](http://www.lupusresearch.org/news-and-events/press-releases/til.html)
+
+3. Institution specific funding
+
+## Track Record of Funding
+
+The projects that I am proposing have a strong track record of being
+funded by both the NIH and the Alliance for Lupus Research.
+
+# Wider impact of research agenda
+
+
+My research will identify genetic variants and pathways underlying SLE
+and other important human diseases, leading to better methodologies
+for both the diagnosis and treatment of those diseases, and resulting
+in significant decreases is patient morbidity and mortality.
+Secondarily, the tools that I develop to effect this work will enable
+researchers in other fields to more rapidly and cheaply identify
+relevant factors for economically and environmentally important
+phenotypes, such as pathogen-resistance in crops or
+disease-susceptibility in thylocenes. Furthermore, as all of my tools
+will be released under Open Source licenses, external researchers will
+be able to build upon and improve my tools without being forced to
+reinvent them.
+
+
+[^Armstrong2009:sle_gi]: D L Armstrong et al. “Identification of new SLE-associated genes with a two-step
+ Bayesian study design”. In: Genes Immun. 10.5 (July 2009), pp. 446–456. doi:
+ [10.1038/gene.2009.38](http://dx.doi.org/10.1038/gene.2009.38).
+
+[^Armstrong2008:function2gene]: Don L Armstrong, Chaim O Jacob, and Raphael Zidovetzki. “Function2Gene: a
+ gene selection tool to increase the power of genetic association studies by utilizing
+ public databases and expert knowledge”. In: BMC Bioinformatics 9 (2008), p. 311.
+ doi: [10.1186/1471-2105-9-311](http://dx.doi.org/10.1186/1471-2105-9-311).
+
+[^Jacob2009:sle_irak1]: Chaim O Jacob et al. “Identification of IRAK1 as a risk gene with critical role
+ in the pathogenesis of systemic lupus erythematosus”. In: Proc. Natl. Acad. Sci.
+ U.S.A. 106.15 (Apr. 2009), pp. 6256–6261. doi: [10.1073/pnas.0901181106](http://dx.doi.org/10.1073/pnas.0901181106).
+
+[^Jacob2007:ar_lupus]: Chaim O Jacob et al. “Identification of novel susceptibility genes in childhood-
+ onset systemic lupus erythematosus using a uniquely designed candidate gene
+ pathway platform”. In: Arthritis Rheum. 56.12 (Dec. 2007), pp. 4164–4173. doi:
+ [10.1002/art.23060](http://dx.doi.org/10.1002/art.23060).
+
+[^Jacob2012:sle_ncf2]: Chaim O Jacob et al. “Lupus-associated causal mutation in neutrophil cytosolic
+ factor 2 (NCF2) brings unique insights to the structure and function of NADPH
+ oxidase”. In: Proc. Natl. Acad. Sci. U.S.A. 109.2 (Jan. 2012), pp. 59–67. doi:
+ [10.1073/pnas.1113251108](http://dx.doi.org/10.1073/pnas.1113251108).
+
+[^Stapleton2011:thbs1]: Christopher J Stapleton et al.
+ “Thrombospondin-1 modulates the angiogenic phe- notype of human
+ cerebral arteriovenous malformation endothelial cells”. In:
+ Neurosurgery 68.5 (May 2011), pp. 1342–1353.
+ doi: [10.1227/NEU.0b013e31820c0a68](http://dx.doi.org/10.1227/NEU.0b013e31820c0a68).
+
+[^survival_rate]: Only 4% of patients survive to 5 years after diagnosis
+
+[^avm_definition]: Direct artery to vein connection without an
+ intervening capilary bed; leads to high pressure arterial flow in
+ venous tissue and can lead to hemmorrhage and death.
+
+[^extending_note]: and extending existing open source tools where they
+ exist
+
--- /dev/null
+[[!meta title="Teaching Statement"]]
+
+# Why I teach
+
+I have always wanted to know how everything works, interconnects, and
+evolved. That moment when a flash of insight shines a light on the
+underlying structure of nature is an incredible feeling. Like many
+researchers in science, I willingly subject myself to experimental
+failures, difficult-to-interpret results, funding difficulties, and
+long hours in order to receive that momentary feeling.
+
+I teach because I want to share the excitement of discovery and
+knowing, and I want others to be able to experience that excitement
+for themselves. It is also quite rewarding to see the glimmer of
+insight in my students eyes when they finally reach understanding for
+themselves.
+
+# General Goals for Students
+
+## Desire and Excitement
+
+If my students are *only* interested in learning the material I am
+teaching to earn credit, then I have failed as a teacher. I want to
+covey at least some of my excitement in the subject to them.
+Perhaps it's naïve, but I think that once students are excited about
+the material, they are more likely to succeed.
+
+## Informed Skepticism
+
+While only a small percentage of my students will become scientists, I
+want them all to know how science works, how to analyze claims, weigh
+evidence, do background research, and come to an independent
+understanding of nature. From politics to the latest false claim on
+the Internet, an ability to become informed, think critically, and
+analyze skeptically will help my students be conscientious members of
+our democratic society.
+
+# How I Teach
+
+## Task Analysis
+
+
+For each course, I identify course-specific overall goals that I want
+all of my students to achieve. Then, I plan a path to these goals,
+with a hierarchy of sub-goals along the way. This enables me to
+measure the effectiveness of my teaching and the students' progress at
+each step during the course. For example, in an introductory
+bioinformatics course, an overall goal might be to have students be
+able to use common bioinformatic databases to answer biological
+questions. A corresponding sub goal would be for students to be able
+to use dbSNP to select all genetic variants in a specific gene in a
+specific organism.
+
+## Learn By Doing
+
+Even though lecturing, demonstrations, and similar passive learning
+techniques are important, everyone learns best by doing. Mistakes,
+failure, experimentation, and learning from them are important parts
+of learning by doing, just as they are in science. To the greatest
+extent possible, I want to provide opportunities for students to learn
+by doing. I want students to learn by solving problems using the
+knowledge and resources they have gained in the course.
+
+## Individual Engagement
+
+In large courses it is very difficult to keep individual students
+engaged, as they feel they are just one face in a hundred and have
+limited opportunities to ask questions. When lecturing, I like to
+combat this by asking students questions directly, and getting
+students (even those at the back) to participate in demonstrations. I
+will also be accessible both in-person on campus, and via e-mail.
+Finally, I will encourage my teaching assistants (TAs) to be engaged
+with our students by asking TAs about students in their sections in TA
+meetings.
+
+## Students Teaching Others
+
+
+Having every student engaged with a teacher is a laudable goal, and
+may be achievable in small in large ones, there will always
+be some people who are not reached. Students teaching other students
+is one method of extending a teacher's reach. In the past, I have had
+online forums or mailing lists for all courses that I have taught. In
+these forums, students are able to ask questions, and other students
+are able to answer them. In addition, students are able to reinforce
+their learning by answering other student's questions. You know a
+concept when you can teach others.
+
+## Technology
+
+Classroom technology is very useful in increasing the ability of
+students to learn, experiment, and measuring outcomes in the
+classroom. I plan on using:
+
+1. Interactive websites to enable student's active learning by doing,
+ including exercises, experiments, and other activities.
+
+2. Real-time online feedback using automated grading on a website to
+ the extent possible on homework so students know whether they
+ understand the material.
+
+3. In-lecture questions through clickers or smart phones when the
+ course is too large to gauge student understanding of material by
+ asking questions of students or raising hands.
+
+4. Recording lectures so that students (and I) can refer to them
+ later.
+
+5. Forums, mailing lists, and other communication methods so that
+ students can learn cooperatively. When students explain material to
+ other students, it answers other student's questions and reinforces
+ their own knowledge.
+
+6. Demonstrations in class and online, both real and simulated, when
+ appropriate to the material being taught.
+
+# Measuring Outcomes
+
+## Success and Failure
+
+I'm continuing to study how to be a more effective teacher by learning
+from other teachers and research into teaching techniques, and will
+continue to do that as long as I teach. I will measure the outcomes of
+my teaching in order to determine how effective I am. By correlating
+the teaching methods I use for each sub-goal of my course with student
+outcomes, over time I can identify the most effective teaching
+strategies for me.
+
+# Teaching Experiences
+
+## Teaching Assistant
+
+While a graduate student at UC Riverside, I was a teaching assistant
+for
+[Introductory Biology, Introductory Genetics, Molecular Biology, and Developmental Biology.](http://www.biology.ucr.edu/courses/UGcourses.html)
-[[!if test="enabled(calendar)" then="""
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-
-<!-- [[Thoughts]] -->
-
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[[Projects]]
[[Archives]]
+[[!if test="enabled(calendar)" then="""
+[[!calendar pages="./posts/* and !*/Discussion"]]
+"""]]
+
+
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+<TMPL_IF HTML5><section id="comments"><TMPL_ELSE><div id="comments"></TMPL_IF>
+<TMPL_VAR COMMENTS>
+<TMPL_IF ADDCOMMENTURL>
+<div class="addcomment">
+<a href="<TMPL_VAR ADDCOMMENTURL>">Add a comment</a>
+</div>
+<TMPL_ELSE>
+<div class="addcomment">Comments on this page are closed.</div>
+</TMPL_IF>
+<TMPL_IF HTML5></section><TMPL_ELSE></div></TMPL_IF>
+</TMPL_IF>
+</TMPL_UNLESS>
+
+</div>
+
+<TMPL_IF HTML5><footer id="footer" class="pagefooter"><TMPL_ELSE><div id="footer" class="pagefooter"></TMPL_IF>
+<TMPL_UNLESS DYNAMIC>
+<TMPL_IF HTML5><nav id="pageinfo"><TMPL_ELSE><div id="pageinfo"></TMPL_IF>
+
+<TMPL_VAR TRAILS>
+
+<TMPL_IF TAGS>
+<TMPL_IF HTML5><nav class="tags"><TMPL_ELSE><div class="tags"></TMPL_IF>
+Tags:
+<TMPL_LOOP TAGS>
+<TMPL_VAR LINK>
+</TMPL_LOOP>
+<TMPL_IF HTML5></nav><TMPL_ELSE></div></TMPL_IF>
+</TMPL_IF>
+
+<TMPL_IF BACKLINKS>
+<TMPL_IF HTML5><nav id="backlinks"><TMPL_ELSE><div id="backlinks"></TMPL_IF>
+Links:
+<TMPL_LOOP BACKLINKS>
+<a href="<TMPL_VAR URL>"><TMPL_VAR PAGE></a>
+</TMPL_LOOP>
+<TMPL_IF MORE_BACKLINKS>
+<span class="popup">...
+<span class="balloon">
+<TMPL_LOOP MORE_BACKLINKS>
+<a href="<TMPL_VAR URL>"><TMPL_VAR PAGE></a>
+</TMPL_LOOP>
+</span>
+</span>
+</TMPL_IF>
+<TMPL_IF HTML5></nav><TMPL_ELSE></div></TMPL_IF>
+</TMPL_IF>
+
+<TMPL_IF COPYRIGHT>
+<div class="pagecopyright">
+<a name="pagecopyright"></a>
+<TMPL_VAR COPYRIGHT>
+</div>
+</TMPL_IF>
+
+<TMPL_IF LICENSE>
+<div class="pagelicense">
+<a name="pagelicense"></a>
+License: <TMPL_VAR LICENSE>
+</div>
+</TMPL_IF>
+
+<div class="pagedate">
+Last edited <TMPL_VAR MTIME>
+<!-- Created <TMPL_VAR CTIME> -->
+</div>
+
+<TMPL_IF HTML5></nav><TMPL_ELSE></div></TMPL_IF>
+<TMPL_IF EXTRAFOOTER><TMPL_VAR EXTRAFOOTER></TMPL_IF>
+</TMPL_UNLESS>
+<!-- from <TMPL_VAR WIKINAME> -->
+<TMPL_IF HTML5></footer><TMPL_ELSE></div></TMPL_IF>
+
+<TMPL_IF HTML5></article><TMPL_ELSE></div></TMPL_IF>
+
+</body>
+</html>
projects / don.git / commitdiff
