From 1a6091b23751e5be8dd70369fc87e612de327bc9 Mon Sep 17 00:00:00 2001 From: Alexander Kabui Date: Fri, 7 May 2021 00:54:03 +0300 Subject: replace relative img path --- .../Wang_WIlliams_Rat_Brain_Proteome_For_Blog.md | 46 ++++++++++++++++------ 1 file changed, 33 insertions(+), 13 deletions(-) diff --git a/blog/2021/proteome/Wang_WIlliams_Rat_Brain_Proteome_For_Blog.md b/blog/2021/proteome/Wang_WIlliams_Rat_Brain_Proteome_For_Blog.md index b29d28b..8f28873 100644 --- a/blog/2021/proteome/Wang_WIlliams_Rat_Brain_Proteome_For_Blog.md +++ b/blog/2021/proteome/Wang_WIlliams_Rat_Brain_Proteome_For_Blog.md @@ -68,7 +68,10 @@ End of context; on with the topic at hand: One small molecule of great fame--DOPAMINE--and its modulation, variation, and contribution to addiction -![](media/image1.png) + +Dopamine + + THE BIG QUESTION: **What proteins related to dopamine and its many roles in behavior are strongly modulated by DNA variants, and can we determine what gene variants are related both to dopamine function and substance use disorders. ** > @@ -95,7 +98,7 @@ There are two ways to do this: to [***https://www.genenetwork.org***](https://www.genenetwork.org) and set up the **Select and search **screen to look as shown below: -![](media/image2.png) +Select and search Note that in the **Combined** field above, I have entered the string @@ -127,7 +130,9 @@ linked to *dopamine* AND that have reasonable genetic linkage in the HXB family to a particular genome coordinate (usually a SNP). The **Search Results** table should look like the screenshot below.  -![](media/image3.png) + +Search Results + I have highlighted the row 8--the ARNTL protein--a major transcription factor involved in circadian rhythms that is upregulated by DRD2 @@ -140,7 +145,9 @@ screenshot below I have scrolled over to the right to display the **Peak Location** column after having performing the sort. All of these proteins map to Chr 1 at about 43.7 megabases (Mb). -![](media/image4.png) + +Search Results + We see ARNTL again and eight other proteins that are genetically downstream of one or many DNA variants located on the proximal part of @@ -166,7 +173,9 @@ window, or you can just paste this URL command into a browser: If all goes well, your browser will display this content (and much more too): -![](media/image5.png) + +mapping + Before we map SYT7 protein expression, you may be curious to know how @@ -175,7 +184,9 @@ this protein has been linked to dopamine.  The answer is one click away. Tap on the **GeneWiki** button, highlighted below in grey. -![](media/image6.png) + + + A **GeneWiki** window will open, and RIF number 18 explains the association with *dopamine* and also links to a 2011 paper (PMID @@ -187,7 +198,7 @@ Again we pause briefly for \"data due diligence\". In the **Statistics** levels in 21 strains has a hint of bimodality--that is a good thing. Bimodality worked well for Gregor Mendel, and may work well for us. - + There are no outliers, so we can map these logged protein expression data \"as given\" without further normalization. @@ -199,7 +210,9 @@ updated GEMMA linear mixed model mapping function in GeneNetwork. Open the **Mapping Tools** window -![](media/image8.png) + + + In the screenshot above I have mapped variation in SYT7 protein level using the new **Genotypes file: Experimental (smoothed)** @@ -214,13 +227,16 @@ Jonathan, David, Hakan, Tristan, Victor, Jun, many others\....). The Manhattan plot of variation in SYT7 protein expression should look like this:  -![](media/image9.png) + + + Beneath the Manahattan plot there is a **Mapping Statistics** table that provides estimates a SNP coordinates (Rnor6 assembly) calculated by GEMMA with -logP values and additive effects (log2 scale). -![](media/image10.png) + + A -logP value of 5.27 is good--normally at or above genome-wide threshold of significance. (This assertion does need more support, and @@ -251,7 +267,8 @@ case. This will generate a chromosome-specific view; part shown below. - + + The QTL peak is a \"non-recombinant\" plateau that extends from 35.5 to 45 Mb---confirming visually what we had already determined from the @@ -263,7 +280,9 @@ You can keep zooming in on a specific region of a chromosome by clicking on the pink horizontal bar alonge the top. Here is the plateau region of the SYT7 protein expression QTL. -![](media/image12.png) + + + As you can tell from the screenshot, there are lots of genes--real and putative--that call this part of Chr 1 home. @@ -356,7 +375,8 @@ Simple--clip out all of those positional candidate genes and paste them into the search **Get Any** window of GeneNetwork. It should look like this: - ![](media/image13.png) + + About 12 of these proteins have reasonably high expression in the rat brain, and three of these also are associated with reasonably strong -- cgit v1.2.3