hokin-pag2017.tex

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\begin{document}

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\veryHuge\color{NCGRBlue} 
\textbf{Integrating Genetic with Genomic Data in Legume InterMines}

\normalsize\color{Black}

\begin{minipage}[c]{188mm}
  \LARGE Sam Hokin, Andrew Farmer \\
  \normalsize \url{shokin@ncgr.org}, \url{adf@ncgr.org}
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  \LARGE Vivek Krishnakumar \\
  \normalsize \url{vkrishna@jcvi.org}
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  \includegraphics[width=40mm]{LegFedSiteLogo.pdf} % LegFed logo
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  %% ----------------------------------------------------------------------------------------
  %% 	ABSTRACT
  %% ----------------------------------------------------------------------------------------

  %% \begin{abstract}
  %% \end{abstract}

  %% ----------------------------------------------------------------------------------------
  %% 	INTRODUCTION
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  \section*{INTRODUCTION}

  \textbf{InterMine} \url{intermine.org} is an open-source, extensible, data warehouse developed by the Micklem Lab at Cambridge with contributions from developers around the world.
  The core app is written for FlyMine \url{flymine.org}, an integrated database for \textit{Drosophila} and \textit{Anopheles} genomics.
  \textbf{The core InterMine data model does not include genetic data}.

  \textbf{The USDA-funded Legume Information System (LIS)} collects and provides both genomic and genetic data for legumes on the main LIS site \url{legumeinfo.org} as well as
  SoyBase \url{soybase.org} and PeanutBase \url{peanutbase.org}. The LIS and PeanutBase sites use the Tripal extension of the Drupal web application, using Chado databases which 
  include genetic data.

  \textbf{The NSF-funded Legume Federation} \\
  \url{legumefederation.org}, in turn, was chartered to to provide a ``one-stop shop'' for legume breeders, geneticists and biologists,
  federating data sources such as LIS \url{legumeinfo.org}, MTGD \url{medicagogenome.org}, and others.
  For that purpose, \textbf{we have extended InterMine to include genetic data} and we have added new visualization and analysis tools.

  \begin{center}
    \includegraphics[width=\figwidth]{genetics-genomics-venn.pdf} % Venn diagram showing markers
    \captionof{figure}{
      Genetic markers are the glue that relate genetic to genomic locations.
    }
  \end{center}

  Genetic data is largely independent of genomic data: genetic features are positioned on linkage groups and measured in centiMorgans (cM), while genomic features are positioned on chromosomes and measured in base pairs (bp).
  \textbf{Genetic markers can have both genetic and genomic locations.} We make use of this to relate genetic features to the genome.

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  %% 	OBJECTIVES
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  \section*{OBJECTIVES}
  
  \begin{enumerate}
  \item Create a convenient environment for plant breeders and biologists to study legume genomic and genetic data.
  \item Provide query and visualization tools to analyze genetic traits along with genomic features.
  \item Enable cross-species analysis amongst legumes and other plants in order to help crop improvement efforts.
  \end{enumerate}

  \color{Black}

  %% ----------------------------------------------------------------------------------------
  %% 	MATERIALS AND METHODS
  %% ----------------------------------------------------------------------------------------

  \section*{DATA MODEL}

  \subsection*{Genetic data}

  In InterMine, data entities are represented by a Java \textbf{Class}, with attributes and references to other \textbf{classes}.
  We have added the following genetic data classes to the core data model:

  \begin{description}

    \item[Germplasm] describes the parents of a cross used in a mapping experiment.

    \item[MappingPopulation] is a container for a mapping experiment: \textbf{parents}, \textbf{geneticMaps}, \textbf{geneticMarkers} and \textbf{genotypingLines}.
      
    \item[GenotypingLine] describes a particular plant line, e.g. a recombinant inbred line, in a \textbf{mappingPopulation}.
      
    \item[GeneticMarker] is a \textbf{SequenceFeature} representing a SNP or other marker, belonging to one or more \textbf{mappingPopulations},
      with a \textbf{chromosomeLocation} as well as \textbf{linkageGroupPositions}.
      It is related to \textbf{QTLs} in the original data sources.
      
    \item[GenotypeValue] is a single value on the markers $\times$ lines genotyping matrix with the value of the parental allele (often denoted by ``A'' or ``B'' or ``H'').
      
    \item[GeneticMap] contains the \textbf{linkageGroups} derived from one or more \textbf{mappingPopulations} (more than one in the case of a consensus map).
      
    \item[LinkageGroup] contains the \textbf{geneticMarkers} and \textbf{QTLs} with their positions and ranges. Each linkage group belongs to one \textbf{geneticMap}.
      
    \item[QTL] is a quantitative trait locus with one or more \textbf{linkageGroupRanges}. It has \textbf{spannedGenes} which overlap its \textbf{associatedMarkers} on the genome.
      (QTL--marker associations are given in the primary data sources, not by comparing the QTL to markers on linkage groups. There are often many more markers within a QTL's genetic range than are explicitly
      associated with that QTL by the researchers.)

  \end{description}

  \subsection*{Genomic data modifications}

  Several additions and extensions to the core InterMine data model are needed to accommodate genomic data pulled from the LIS databases ---
  in particular, Phytozome gene families, as well as the new connection to genetic markers.

  \begin{description}

    \item[Gene] has additional references to \textbf{geneFamily}, \textbf{homologues} and \textbf{spanningQTLs}.

    \item[GeneFamily] describes a Phytozome gene family, referencing a \textbf{consensusRegion}.

    \item[ConsensusRegion] is a \textbf{BioEntity} which holds the sequence associated with a \textbf{geneFamily}.

  \end{description}

  %%----------------------------------------------------------------------------------------
  %%	RESULTS 
  %%----------------------------------------------------------------------------------------

  \section*{VISUALIZATIONS}

  \subsection*{Mapping Populations}

  A genotyping experiment conducted on a mapping population is displayed on the Mapping Population report, with a color-coded \textit{markers $\times$ lines} matrix inspired by Flapjack.

  \begin{center}
    \includegraphics[width=\figwidth]{genotype-matrix.png} % screen grab of mapping population genotype matrix
    \captionof{figure}{
      Two allele exchanges in this mapping population indicate recombination, contributing to a 0.71 cM increase in linkage group distance on the consensus map.
    }
  \end{center}

  One can filter the markers by a single QTL or QTLs with traits that match a search term.

  \subsection*{Linkage Groups}

  Linkage groups are displayed in a horizontal diagram with markers and QTLs shown at their genetic locations. The markers and QTLs link to their report pages.

  \begin{center}
    \includegraphics[width=\figwidth]{linkage-group-diagram.png} % screen grab of a soybean linkage group diagram
    \captionof{figure}{
      Soybean consensus linkage group GMComposite2003\_E has 143 QTLs and 189 markers, 94 of which have been located on chromosome 15.
    }
  \end{center}
  
  The genetic map report page displays the diagrams for all of its linkage groups.

  \section*{PROCESSING}

  A post-processor runs through the QTLs and finds the genes that are located within the range spanned by the QTL's associated markers, if the QTL has more than one. The QTL--marker associations
  are drawn from the original data source (as opposed to using all the markers lying within a QTL's range on a linkage group). Therefore, QTLs which have zero or only one associated marker do not have
  spanned genes.

  \begin{center}
    \includegraphics[width=\figwidth]{genetic-marker-jbrowse.png} % screen grab of markers and genes on a JBrowse
    \captionof{figure}{
      Soybean QTL Seed oil plus protein 1-5 is flanked by Satt151 and Satt263 leading to 21 spanned genes.
    }
    \vspace{24pt}
    \includegraphics[width=\figwidth]{QTL-report.png} % screen grab of QTL report showing markers and spanned genes
    \captionof{figure}{
      Genes spanned by a QTL via its associated markers are determined in a post-processor and linked on the QTL report page.
    }
    \vspace{24pt}
    \includegraphics[width=4in]{gene-seed-oil-query.png} % screen grab of query on genes with spanning QTLs containing Seed oil
    \captionof{figure}{
      This Soymine query returns 7,731 genes spanned by the 29 QTLs containing ``Seed oil'' that have at least two flanking markers.
    }
  \end{center}

  %%----------------------------------------------------------------------------------------
  %%	CONCLUSIONS
  %%----------------------------------------------------------------------------------------

  \section*{NEXT STEPS}

  The Legume Federation hopes to translate discoveries of the genetic basis underlying key traits made in one species 
  to other species, aiding crop improvement efforts across the family.
  We will use InterMine to aggregate trait mapping experiments being performed by plant breeders, augmenting the comparative genomics well underway.

  What data and tools would YOU like to see in a genetic+genomic mine?
  Send us your suggestions at \url{legumefederation.org/contact} or Twitter \textbf{@LegumeFed}.

  %%----------------------------------------------------------------------------------------
  %%	FORTHCOMING RESEARCH
  %%----------------------------------------------------------------------------------------

  %% \section*{Forthcoming Research}

  %% \begin{enumerate}
  %% \item blah
  %% \end{enumerate}

  %%----------------------------------------------------------------------------------------
  %%	REFERENCES
  %%----------------------------------------------------------------------------------------

  \nocite{*} % Print all references regardless of whether they were cited in the poster or not
  \bibliographystyle{plain} % Plain referencing style
  \bibliography{hokin-pag2017} % Use hokin-pag2017.bbl - regenerate with bibtex

  %%----------------------------------------------------------------------------------------
  %%	ACKNOWLEDGEMENTS
  %%----------------------------------------------------------------------------------------

  \subsection*{Acknowledgements}
  
  \noindent \smallish This research was funded by National Science Foundation grant \#1444806.

\end{multicols*}

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