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        <revisions>
          <rev contentformat="text/x-wiki" contentmodel="wikitext" xml:space="preserve">[[File:MarcotteLab-Venn.png||400px|]]


Our group studies the large-scale organization of proteins, essentially trying to reconstruct the 'wiring diagrams' of cells by learning how all of the proteins encoded by a genome are associated into functional pathways, systems, and networks. We are interested both in discovering the functions of the proteins as well as in learning the underlying organizational principles of the networks. The work is evenly split between computational and experimental approaches, with the latter tending to be high-throughput functional genomics and proteomics approaches for studying thousands of genes/proteins in parallel.

== A few of our current projects ==

[[File:MarcotteLab-OneSlideSummary-8-2020-bottom.jpg||600px|]]

&lt;br&gt;&amp; a few of the various systems we've studied (or tried to)...

[[File:Orgs1.png||400px|||]]

== Bioinformatics of protein function and interactions ==

We've discovered a number of features of genomes that allow us to predict functions for proteins that have never been experimentally characterized. Using these techniques and information from over 30 fully sequenced genomes, we were able to calculate some of the first genome-wide predictions of protein function, finding very preliminary function for over half the 2,500 uncharacterized genes of yeast. Now, with thousands of genomes in hand, we're extending these techniques, as well as asking fundamental questions about the evolution of protein interactions and the evolution of genomes. 

[[File:Orgs2.png||200px|right]]


''Some of our recent papers on gene networks and the systematic discovery of gene function include:''&lt;br&gt;
{{Paper
|title=RIDDLE: Reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network
|authors=Wang, Hwang, ''et al.''
|journal=Genome Biology
|pubmed=23268829
|volume=13(12)
|page=R125
|link=http://genomebiology.com/2012/13/12/R125/abstract
|pub_year=2012
}}

{{Paper
|title=Predicting genetic modifier loci using functional gene networks
|authors=Lee, Lehner, ''et al.''
|journal=Genome Research
|pub_year=2010
|volume=20
|page=1143-1153
|pubmed=20538624
|pdf=GenomeResearch_GeneticModifiers_2010.pdf
|link=http://dx.doi.org/10.1101/gr.102749.109
}}

{{Paper
|title=Characterising and predicting haploinsufficiency in the human genome
|authors=Huang ''et al.''
|journal=PLoS Genetics
|pub_year=2010
|volume=6(10)
|pdf=PLoSGenetics_Haploinsufficiency_2010.pdf
|link=http://dx.doi.org/10.1371/journal.pgen.1001154 
|page=e1001154
|pubmed=20976243
}}

{{Paper
|title=A single gene network accurately predicts phenotypic effects of gene perturbation in ''Caenorhabditis elegans''
|authors=Lee, Lehner ''et al.''
|journal=Nature Genetics
|pub_year=2008
|volume=40(2)
|page=181-8
|pubmed=18223650
|link=http://www.nature.com/ng/journal/v40/n2/abs/ng.2007.70.html
|comment=
}}

{{Paper
|title=A critical assessment of ''Mus musculus'' gene function prediction using integrated genomic evidence
|authors=Peña-Castillo ''et al.''
|journal=Genome Biology
|pub_year=2008
|volume=9 Suppl 1
|page=S2
|pubmed=18613946 
|link=http://genomebiology.com/2008/9/S1/S2
|comment=
}}

{{Paper
|title=A high-accuracy consensus map of yeast protein complexes reveals modular nature of gene essentiality
|authors=Hart ''et al.''
|journal=BMC Bioinformatics
|pub_year=2007
|volume=8
|page=236.
|pubmed=17605818 
|link=http://www.biomedcentral.com/1471-2105/8/236
|comment=
}}

{{Paper
|title=A probabilistic functional network of yeast genes
|authors=Lee ''et al.''
|journal=Science 
|pub_year=2004
|volume=306(5701)
|page=1555-8.
|pubmed=15567862 
|link=http://www.sciencemag.org/cgi/content/full/306/5701/1555
|comment=
}}

{{Paper
|title=A probabilistic view of gene function
|authors=Fraser, Marcotte
|journal=Nature Genetics
|pub_year=2004
|volume=36(6)
|page=559-64
|pubmed=15167932 
|link=http://www.nature.com/ng/journal/v36/n6/abs/ng1370.html
|comment=
}}


Link to our large-scale gene networks for yeast, worms, mouse, ''Arabidopsis'': http://www.functionalnet.org. An illustration of our ''Arabidopsis'' gene network won Honorable Mention in the 2010 [http://www.marcottelab.org/paper-pdfs/848.full.pdf ''Science'' Visualization Challenge] &amp; was featured by the [http://www.nytimes.com/slideshow/2011/02/17/science/20110217-visualize-6.html ''New York Times'']

Link to some of our public bioinformatics resources: http://bioinformatics.icmb.utexas.edu

== Rational identification of genes affecting traits and diseases ==

Using the gene networks and other computational tools, we've now gained some ability to rationally predict the consequences to an organism of mutating or interrupting a specific gene. This means that by using these tools, we can often select a small set of candidate genes to be implicated in a particular disease or trait. We've now experimentally validated &gt;300 such candidate genes for diverse traits in a wide range of organisms, including yeast, worms, ''Arabidopsis'', ''C. elegans'', frogs, mice, and humans. For example, in yeast we've used network models to discover a large number of new ribosome biogenesis genes (collaborating with [http://www.bio.utexas.edu/faculty/ajohnson/index.htm Arlen Johnson]), as well as genes controlling such features as cell size. In animals, e.g. using our worm gene network models developed with collaborators [http://www.crg.es/ben_lehner Ben Lehner] and [http://www.fraserlab.org/ Andy Fraser], we could successfully identify new genes controlling longevity, as well as genes capable of suppressing the loss of the Retinoblastoma tumor suppressor, thus 'curing' worms of model tumors. In ''Arabidopsis'', with now ex-postdoc [http://polaris.icmb.utexas.edu/people/il1001/author.htm Insuk Lee] and collaborator [http://carnegiedpb.stanford.edu/rhee-lab Sue Rhee], we could rationally identify new genes regulating root growth, drought resistance, and seedling pigmentation. In vertebrates, working with the [http://www.bio.utexas.edu/faculty/wallingford/ Wallingford] and [http://gene.tamu.edu/faculty_pages/faculty_FinnellR.php Finnell] labs, we've been able to use gene network models to help assign functions to a birth defect gene, as well as to identify entirely new birth defect genes, confirming their roles ''in vivo''. [[File:worm-synmuv.jpg||300px|right]] 

''Some of our recent papers on the rational association of genes with traits and diseases:''&lt;br&gt;

{{Paper
|title=Coordinated genomic control of ciliogenesis and cell movement by Rfx2
|authors=Chung, Kwon ''et al.''
|journal=eLife
|pubmed=24424412
|pdf=eLife_RFX2_2014.pdf
|volume=3
|page=e01439
|link=http://dx.doi.org/10.7554/eLife.01439
|pub_year=2014
}}

{{Paper
|title=Evolutionarily Repurposed Networks Reveal the Well-Known Antifungal Drug Thiabendazole to Be a Novel Vascular Disrupting Agent
|authors=Cha ''et al.''
|journal=PLoS Biology
|pubmed=
|volume=10(8)
|link=http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001379
|pdf=PLoSBiology_TBZ_2012.pdf
|page=e1001379
|pub_year=2012
|comment=[http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001380 Synopsis] [http://www.nytimes.com/2012/08/21/health/research/clues-to-fighting-cancer-are-found-in-the-genes-of-yeast.html NY Times] [http://publications.nigms.nih.gov/multimedia/repurposing-genes-drugs.html NIGMS video]
}}

{{Paper
|title=Prioritizing candidate disease genes by network-based boosting of genome-wide association data
|authors=Lee, Blom, ''et al.''
|journal=Genome Research
|pubmed=21536720
|pub_year=2011
|volume=21(7)
|pdf=GenomeResearch_HumanNet_2011.pdf
|page=1109-21
|link=http://dx.doi.org/10.1101/gr.118992.110
}}

[[File:phenologs.png||150px|left]]

{{Paper
|title=Systematic discovery of nonobvious human disease models through orthologous phenotypes
|authors=McGary, Park ''et al.''
|journal=Proc Natl Acad Sci U S A
|pub_year=2010
|volume=107(14)
|page=6544-9
|pubmed=20308572
|link=http://www.pnas.org/cgi/doi/10.1073/pnas.0910200107
|comment=Carl Zimmer wrote [http://www.nytimes.com/2010/04/27/science/27gene.html?_r=1 a nice story about this work] for ''The New York Times''.
}}

{{Paper
|title=Rational association of genes with traits using a genome-scale gene network for ''Arabidopsis thaliana''
|authors=Lee ''et al.''
|journal=Nature Biotechnology
|pub_year=2010
|volume=28(2)
|page=149-156
|pubmed=20118918
|link=http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1603.html
|comment=
}}

{{Paper
|title=Rational extension of the ribosome biogenesis pathway using network-guided genetics
|authors=Li ''et al.''
|journal=PLoS Biology
|pub_year=2009
|volume=7(10) 
|page=e1000213
|pubmed=19806183
|link=http://dx.doi.org/10.1371/journal.pbio.1000213
|comment=
}}

{{Paper
|title=The planar cell polarity effector protein Fuzzy is essential for targeted membrane trafficking, ciliogenesis, and mouse embryonic development
|authors=Gray ''et al.''
|journal=Nature Cell Biology
|pub_year=2009
|volume=11(10)
|page=1225-32
|pubmed=19767740
|link=http://dx.doi.org/10.1038/ncb1966
|comment=
}}

{{Paper
|title=A single gene network accurately predicts phenotypic effects of gene perturbation in ''Caenorhabditis elegans''
|authors=Lee, Lehner ''et al.''
|journal=Nature Genetics
|pub_year=2008
|volume=40(2)
|page=181-8
|pubmed=18223650
|link=http://www.nature.com/ng/journal/v40/n2/abs/ng.2007.70.html
|comment=
}}

{{Paper
|title=Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export of pre-40S subunits
|authors=White ''et al.''
|journal=Mol Cell Biol
|pub_year=2008
|volume=28(10)
|page=3151-61
|pubmed=18332120
|link=http://mcb.asm.org/cgi/content/full/28/10/3151
|comment=
}}

{{Paper
|title=Broad network-based predictability of ''Saccharomyces cerevisiae'' gene loss-of-function phenotypes
|authors=McGary ''et al.''
|journal=Genome Biology
|pub_year=2007
|volume=8(12)
|page=R258.
|pubmed=18053250 
|link=http://genomebiology.com/2007/8/12/R258
|comment=
}}



Use our ''phenolog'' method to link genes to traits: http://www.phenologs.org

Read more about some of our [http://www.bio.utexas.edu/faculty/wallingford/Pages/Research.html#Computation computational approaches to developmental biology] &amp; the UT [http://www.bio.utexas.edu/faculty/wallingford/drbi/ Developmental and Regenerative Biology Initiative]

== Proteomics: High-throughput protein expression and interaction profiling ==

From our work and others, it is apparent that proteins in the cell participate in extended protein interaction networks involving thousands of proteins. By defining these networks, we can not only discover the functions of specific proteins based on their connections, but also use these networks as tools to predict the outcome of perturbing the cell. As part of our research efforts in this area, we have been developing high-throughput methods to measure protein abundances in complex biological samples (e.g., by quantitative shotgun proteomics mass spectrometry) and protein localization with cells (e.g., by high-throughput automated fluorescence microcopy, such as of cell microarrays). These sorts of data help us build a catalog of protein, mRNA and metabolite expression from cells grown under many different conditions, forming a quantitative picture of these molecular events inside cells. We expect that data of these sorts will put us on the road to developing predictive, rather than merely descriptive, theories of biology.

''Recent papers in this area include:''&lt;br&gt;
[[File:PvsSB.jpg||100px|left]]
{{Paper
|title=A pan-plant protein complex map reveals deep conservation and novel assemblies
|authors=McWhite CD, Papoulas O, Drew K, Cox RM, June V, Dong OX, Kwon T, Wan C, Salmi ML, Roux, SJ Jr., Browning KS, Chen ZJ, Ronald PC, Marcotte EM
|journal=Cell
|pub_year=2020
|volume=181(2)
|pubmed=32191846
|page=460-474.e14
|link=https://doi.org/10.1016/j.cell.2020.02.049
|pdf=Cell_PlantComplexes_2020.pdf
}}

{{Paper
|title=Panorama of ancient metazoan macromolecular complexes
|authors=Wan, Borgeson ''et al.''
|journal=Nature
|pubmed=26344197
|volume=525
|page=339–344
|link=http://dx.doi.org/10.1038/nature14877
|pdf=Nature_AnimalComplexes_2015.pdf
|pub_year=2015
}}

{{Paper
|title=Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response
|authors=Wine, Boutz, Lavinder ''et al.''
|journal=Proc Natl Acad Sci USA 
|pubmed=23382245
|volume=110(8)
|page=2993–2998
|pdf=PNAS_IgGProfiling_2013.pdf
|pub_year=2013
|link=http://www.pnas.org/content/early/2013/02/01/1213737110.abstract  
}}

{{Paper
|title=Census of Human Soluble Protein Complexes
|authors=Havugimana ''et al.''
|journal=Cell
|pubmed=22939629
|volume=150
|page=1068-1081
|link=http://www.cell.com/abstract/S0092-8674%2812%2901006-9
|pdf=Cell_HumanProteinComplexes_2012.pdf
|pub_year=2012
}}

{{Paper
|title=Insights into the regulation of protein abundance from proteomic and transcriptomic analyses  
|authors=Vogel &amp; Marcotte
|journal=Nature Reviews Genetics
|pubmed=22411467
|volume=13
|link=http://dx.doi.org/10.1038/nrg3185
|pdf=NatureReviewsGenetics_ProteinAbundanceRegulation_2012.pdf
|page=227-232
|pub_year=2012
}}

{{Paper
|title=Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line
|authors=Vogel ''et al.''
|journal=Molecular Systems Biology
|pub_year=2010
|pubmed=20739923
|volume=6
|page=article 400
|pdf=MolecularSystemsBiology_2010_HumanProteomics.pdf
|link=http://www.nature.com/msb/journal/v6/n1/full/msb201059.html
|comment=[http://www.marcottelab.org/paper-pdfs/MolecularSystemsBiology_2010_HumanProteomics_NewsAndViews.pdf News and Views]
}}

{{Paper
|title=Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation
|authors=Narayanaswamy ''et al.''
|journal=Proc Natl Acad Sci U S A
|pub_year=2009
|volume=106(25)
|page=10147-52
|pubmed=19502427 
|link=http://www.pnas.org/content/106/25/10147.long
|comment=
}}

{{Paper
|title=Calculating absolute and relative protein abundance from mass spectrometry-based protein expression data
|authors=Vogel, Marcotte
|journal=Nature Protocols
|pub_year=2008
|volume=3(9)
|page=1444-51.
|pubmed=18772871
|link=http://www.nature.com/nprot/journal/v3/n9/abs/nprot.2008.132.html
|comment=Journal website
|link=http://www.marcottelab.org/APEX_Protocol/
|comment=[http://www.marcottelab.org/APEX_Protocol/ Protocol website]
}}

{{Paper
|title=A map of human protein interactions derived from co-expression of human mRNAs and their orthologs
|authors=Ramani ''et al.''
|journal=Molecular Systems Biology
|pub_year=2008
|volume=4
|page=180
|pubmed=18414481
|link=http://www.nature.com/msb/journal/v4/n1/full/msb200819.html
|comment=
}}

{{Paper
|title=Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation
|authors=Lu, Vogel, Wong ''et al.''
|journal=Nature Biotechnology
|pub_year=2007
|volume=25(1)
|page=117-24
|pubmed=17187058
|link=http://www.nature.com/nbt/journal/v25/n1/abs/nbt1270.html
|comment=
}}

&lt;br&gt;
Links to our MS/MS data repositories: http://www.marcottelab.org/MSdata/ and http://www.marcottelab.org/index.php/Category:MSdata [[File:Ciliopathy.png||250px|right]]

Link to the Hu.MAP 2.0 human protein complex map: http://humap2.proteincomplexes.org/ 

Link to the APEX Protocol website: http://marcottelab.org/APEX_Protocol/

Link to the APEX software tool: http://pfgrc.jcvi.org/index.php/bioinformatics/apex.html

Link to the MSpresso website: http://www.marcottelab.org/MSpresso/

Link to the MSblender website: http://www.marcottelab.org/index.php/MSblender  &lt;br&gt;MSblender is proving to be a particularly powerful tool for interpreting mass spectrometry proteomics datasets; we've now used it for thousands of individual datasets.
&lt;br&gt;
&lt;br&gt;

== Recent research news ==
&lt;div style=&quot;border:solid green;margin:8px;padding:10px;&quot;&gt;
[[File:Xenopus-PV.jpg||100px|left]] &lt;br&gt;
'''Read about our [[Texas Xenopus Genome Project]]''', a collaboration with the [http://www.bio.utexas.edu/faculty/wallingford/ Wallingford lab] and the [https://wikis.utexas.edu/display/GSAF/Home+Page UT Genomic Sequencing and Analysis Facility], funded by the [http://www.ti3d.utexas.edu/ Texas Institute for Drug and Diagnostic Development]&lt;br&gt;
&lt;br&gt;
&lt;br&gt;

&lt;/div&gt;</rev>
        </revisions>
      </page>
      <page pageid="62" ns="0" title="SciRuby">
        <revisions>
          <rev contentformat="text/x-wiki" contentmodel="wikitext" xml:space="preserve">== The Manifesto ==

Ruby has no equivalent to the beautifully constructed numpy, scipy, and matplotlib libraries for Python. We believe that the time for a Ruby science and visualization package has come and gone. Sometimes when a solution of sugar and water becomes super-saturated, from it precipitates a pure, delicious, and diabetes-inducing crystal of sweetness, induced by no more than the tap of a finger. So it is, we believe, with the need for numeric and visualization libraries in Ruby.

We are not [http://codeforpeople.com/ the first] with this idea, but we want to bring it to life.

As a further note, we believe that Ruby scripts are no different from the methods used in a mechanical experiment (e.g., the wetlab), and must be published along with any ''published'' derivative experimental results. The license for SciRuby shall likely reflect this, ultimately.

=== Who We Are ===
We are [http://www.ruby-lang.org/ Rubyists], lovers of [http://mislav.uniqpath.com/poignant-guide/ chunky bacon], and [http://en.wikipedia.org/wiki/Science scientists]. Driven mad by the glee of our [http://www.scipy.org/ Python-loving colleagues], we came together [http://kids.niehs.nih.gov/lyrics/peopsing.htm humming Les Mis].

You should join us! [https://spreadsheets.google.com/viewform?formkey=dG80STQzNjBwbHotTjBDUTNIUUVzOWc6MQ Sign up by filling out this form].

Currently, we are:
* [http://www.chem.byu.edu/users/jtprince John T. Prince], Department of Chemistry &amp; Biochemistry, Brigham Young University
* [http://github.com/mohawkjohn John O. Woods], Marcotte Lab, The University of Texas at Austin

=== Why Ruby? ===
First and least, Ruby is a language with a sense of humor.

But more importantly, numerical computation and visualization can be done much better in Ruby, for a number of reasons:

# ''Everything returns a value.'' Ruby's better object model means better of chaining of computation.
# ''Iterators'' are way better than ''for'' loops.
# ''Readability.'' Ruby is incredibly readable, which makes it uber-maintainable.
# ''Metaprogramming.'' Sometimes the simplest solution is to write a [http://github.com/wycats/thor code generator]. Sometimes, [http://banisterfiend.wordpress.com/2008/10/06/metaprogramming-in-the-ruby-c-api-part-two-dynamic-methods/ eigenclasses] are the cleanest. &lt;!-- I wish there was a ruby-lang link for this, some sort of official doc (JW) --&gt;
# ''Integration into Rails.'' The influence of Rails on Ruby is undeniable. Web-based visualization for scientific projects is the future.
# ''R is nice but clunky.'' The learning curve is enormous. It does some things very well, and others not very well at all.

=== Alternatives and Sources of Inspiration ===
* [http://github.com/alexgutteridge/rsruby rsruby], [http://rinruby.ddahl.org/ rinruby], [http://github.com/jtprince/simpler simpler]: gems which connect Ruby to R
* [http://github.com/xdotcommer/flotomatic flotomatic]: Rails gem for the Flot Javascript library, for web data visualization.
* [http://narray.rubyforge.org/ NArray]: Numerical Ruby NArray and Ruby/PGPLOT.
* [http://rb-gsl.rubyforge.org/ Ruby GSL]: Ruby interface for the GNU Scientific Library

== Directives ==

=== Prime Directive ===

All published results obtained using our libraries must include online publication of any and all source code using our libraries.

=== Numeric Array and Matrix Library ===

For what it is worth, the broad success of python is due, in large part, to its numerical computing core, [http://numpy.scipy.org/ numpy].  A few examples: [http://code.google.com/p/h5py/ h5py], [http://www.pymol.org/ pymol], [http://code.google.com/p/mdanalysis/ mdanalysis],...

Goals: Stable, robust, fast, extremely well-documented core numerical library.
* FFI (C) or Rice (C++ with Boost)
** Allow for custom C functions with FFI or Rice.
* Good at casting
* Consider [http://docs.scipy.org/doc/numpy/reference/ufuncs.html#broadcasting broadcasting]
* Thoroughly documented, on par with [http://www.yaml.org/YAML_for_ruby.html Yaml Cookbook]
* Convenience wrappers for GSL, perhaps in a separate module.
* Eventual inclusion in Ruby core.

NArray is a fantastic library that has served the community for many years.  Can it be extended and better documented, or is it better to start from scratch (borrowing conceptually from NArray where we can) using an FFI or Rice interface?

=== Visualization and Plotting Library ===

Goals: High-quality, ''interactive'', dynamic visualizations of the sort seen in [http://processing.org/ Processing] and [http://vis.stanford.edu/protovis/ Protovis].

Currently, the plan is to build a Ruby DSL for creating Protovis plots. This will allow us to produce a variety of image formats, including SVGs, and make visualization fully realizable on the Web.</rev>
        </revisions>
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