@@ -1,7 +1,7 @@

 ---

 title: "Introduction to KEGGlincs"

 author: "Shana White"

-date: "9/30/2016"

+date: "03/23/2017"

 ---

 by [Shana White](https://github.com/shanawhite-UC)

@@ -9,25 +9,18 @@ by [Shana White](https://github.com/shanawhite-UC)

 Installation:

 ```{r}

-#In order to avoid unnecessary warnings, check for installation of devtools (>= 1.12.0):

-packageVersion("devtools")

-[1] ‘1.12.0’

-

 #Make sure that the following bioconductor packages are installed

 source("http://bioconductor.org/biocLite.R")

-biocLite(c("hgu133a.db", "KEGGgraph", "KEGGREST"))

-

-#Companion data package (L1000 Knock-out data and baseline expression data)

-devtools::install_git("https://github.com/shanawhite-UC/KOdata")

+biocLite(c("hgu133a.db", "KEGGgraph", "KEGGREST", "KOdata"))

-#Main package

-devtools::install_git("https://github.com/shanawhite-UC/KEGGlincs")

+#Download package

+biocLite("KEGGlincs")

 #Load/activate package for use

 library(KEGGlincs)

 ```

-#Overview of package

+# Overview of package

 ![](https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/KEGGlincs_overview.jpeg)

@@ -35,24 +28,24 @@ library(KEGGlincs)

 KEGGlincs is an R package that provides a seamless interface for viewing detailed versions of KEGG pathways in Cytoscape such that the exact relationships (*edges*) that exist between pathway elements (*nodes*) are visualized in a meaningful manner.  

 This package is intended to be used as a tool to accurately regenerate KEGG pathways with *expanded* edges that are marked-up (in terms of color or color+width) to portray specific *edge attributes*.  Specifically, 

-- the edges are *expanded* to represent all relationships between genes encoded by the [KGML file] (http://www.kegg.jp/kegg/xml/) but not necessarily represented in the original [KEGG] pathway.  This 'expansion' occurs either because:

+- the edges are *expanded* to represent all relationships between genes encoded by the [KGML file](http://www.kegg.jp/kegg/xml/) but not necessarily represented in the original [KEGG] pathway.  This 'expansion' occurs either because:

   - one node may represent many [often paralogous] genes.

   - a node is of type 'group' and represents two or more genes that are part of the same functional complex.

 - the *edge attributes* represented can be specified by the user as either:

   - Functional - the exact *type* and [in some cases] *subtype* of the relationship defined by the KGML file.

-  - Data driven - based on quantitative experimental evidence for gene-gene relationships generated by experimental data.  As an added feature and motivating example, this package gives users an opportunity to use [LINCS L1000 knock-out data] (http://www.lincscloud.org/l1000/) in order to analyze/visualize the pathway edges as they pertain to specific [cell lines] (http://www.lincscloud.org/cell_types/). 

+  - Data driven - based on quantitative experimental evidence for gene-gene relationships generated by experimental data.  As an added feature and motivating example, this package gives users an opportunity to use [LINCS L1000 knock-out data](http://www.lincscloud.org/l1000/) in order to analyze/visualize the pathway edges as they pertain to specific [cell lines](http://www.lincscloud.org/cell_types/). 

-Aside from edge-specific annotation/mark-up, a unique feature of this package lies in the ability for users to generate graph objects in R and send them to [Cytoscape] (http://www.cytoscape.org/) for an interactive visualization experience via utilities developed by the [cyREST team] (https://github.com/idekerlab/cy-rest-R).

+Aside from edge-specific annotation/mark-up, a unique feature of this package lies in the ability for users to generate graph objects in R and send them to [Cytoscape](http://www.cytoscape.org/) for an interactive visualization experience via utilities developed by the [cyREST team](https://github.com/idekerlab/cy-rest-R).

 The following example showcases the ideas described above.

-##Example: p53 pathway

+## Example: p53 pathway

-###Original KEGG pathway:

-![p53 pathway from KEGG website] (http://www.genome.jp/kegg/pathway/hsa/hsa04115.png)

+### Original KEGG pathway:

+![p53 pathway from KEGG website](http://www.genome.jp/kegg/pathway/hsa/hsa04115.png)

-###Using KEGGlincs without adding data: 

-####Detailed pathway visualized in Cytoscape 

+### Using KEGGlincs without adding data: 

+#### Detailed pathway visualized in Cytoscape 

  - Explicitly shows all documented edges

  - Color-coded to easily interpret edge type (i.e. activation, inhibition, etc.)

    - Edge color key: <a><img src="https://cdn.rawgit.com/uc-bd2k/KEGGlincs/master/vignettes/image_files/color_1.svg"/></a>

@@ -61,12 +54,12 @@ The following example showcases the ideas described above.

 ```{r}

 KEGG_lincs("hsa04115")

 ```

-![] (https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_default.jpeg)

+![](https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_default.jpeg)

-###Overlay pathway edges with LINCS data: 

-####Pathway with edge attributes generated from LINCS L1000 knock-out data, *refined* by cell-line specific expression (default option, see below), and visualized in Cytoscape 

+### Overlay pathway edges with LINCS data: 

+#### Pathway with edge attributes generated from LINCS L1000 knock-out data, *refined* by cell-line specific expression (default option, see below), and visualized in Cytoscape 

  - Explicitly shows all documented edges; edges that do not exist in the data appear but are not marked-up for interpretation [of significance].

    - If baseline expression data is available for the selected cell-line, the pathway will be *refined* to only include edges between genes that are expressed in a given cell line.  The nodes for unexpressed genes are colored gray.  

  - Widths: Magnitude of concordance for the edge in the selected cell-type

@@ -75,14 +68,14 @@ KEGG_lincs("hsa04115")

 <a><img src="https://cdn.rawgit.com/uc-bd2k/KEGGlincs/master/vignettes/image_files/color_2.svg"/></a>

-#####Pathway specific to PC3 cell-line (Prostate cancer)

+#### Pathway specific to PC3 cell-line (Prostate cancer)

 ```{r}

 KEGG_lincs("hsa04115", "PC3")

 ```

-![] (https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_PC3.jpeg)

+![](https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_PC3.jpeg)

-#####Pathway specific to HA1E cell-line (Immortalized normal kidney epithelial)

+#### Pathway specific to HA1E cell-line (Immortalized normal kidney epithelial)

 ```{r}

 KEGG_lincs("hsa04115", "HA1E")

 ```

-![] (https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_HA1E.jpeg)

+![](https://github.com/uc-bd2k/KEGGlincs/blob/master/vignettes/image_files/p53_HA1E.jpeg)

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