library("MSnbase")
library("pRoloc")
csvfile <- "../../inst/extdata/courtland2020pepitdedata.csv"
csv <- read.csv(csvfile)
## There are 2 conditions in this dataset
courtland_control <- readMSnSet2(file = csvfile, ecol = grepEcols(csvfile, pattern = "Control", split = ","), skip = 0)
courtland_mutant <- readMSnSet2(file = csvfile, ecol = grepEcols(csvfile, pattern = "Mutant", split = ","), skip = 0)
## Experimental data to add
experiment <- new("MIAPE",
lab = "Soderling",
name = "Tyler",
contact = "tyler",
email = "twesleyb10@gmail.com",
samples = list(
species = "mouse",
operator = "Jamie courtland"
),
title = "Swip Spatial Proteomics",
abstract = "Mutation of the WASH complex subunit, SWIP, is
implicated in human intellectual disability, but the cellular
etiology of this association is unknown. We identify the neuronal
WASH complex proteome, revealing a network of endosomal proteins.
To uncover how dysfunction of endosomal SWIP leads to disease, we
generate a mouse model of the human
WASHC4 c.3056C>G mutation. Quantitative spatial
proteomics analysis of SWIP P1019R mouse brain
reveals that this mutation destabilizes the WASH complex and
uncovers significant perturbations in both endosomal and lysosomal
pathways. Cellular and histological analyses confirm that
SWIP P1019R results in endo-lysosomal disruption
and uncover indicators of neurodegeneration. We find that
SWIP P1019R not only impacts cognition, but also
causes significant progressive motor deficits in mice. Remarkably,
a retrospective analysis of SWIP P1019R patients
confirms motor deficits in humans. Combined, these findings support
the model that WASH complex destabilization, resulting from
SWIP P1019R, drives cognitive and motor
impairments via endo-lysosomal dysfunction in the brain.",
pubMedIds = "",
url = "",
instrumentModel = "Lumos",
instrumentManufacturer = "ThermoScientific",
ionSource = "",
analyser = "Orbitrap",
detectorType = "Orbitrap",
softwareName = "MaxQuant ",
collisionEnergy = "",
dateStamp = "3 January 2018"
)
## Expression data
e <- exprs(courtland_control)
## Experiment info
toName <- paste0(colnames(courtland_control)[1:21])
colnames(e) <- toName
pd <- data.frame(toName,
row.names=colnames(e))
pd <- new("AnnotatedDataFrame", pd)
## feature data
fd <- rownames(e)
fd <- as.data.frame(csv[,1:8])
fd
rownames(fd) <- rownames(e)
fd <- new("AnnotatedDataFrame", fd)
process <- new("MSnProcess",
processing=c(
paste("Loaded on ",date(),".",sep=""),
paste("")),
normalised=FALSE)
courtland_control <- new("MSnSet",
exprs = e,
phenoData = pd,
experimentData = experiment,
featureData = fd)
## summarise to protein level
courtland_control <- combineFeatures(courtland_control, method = "median", fcol = "Accession", na.rm = TRUE)
courtland_control <- MSnbase::normalise(courtland_control, method = "sum")
fData(courtland_control)$markers <- "unknown"
## Expression data
e <- exprs(courtland_mutant)
## Experiment info
toName <- paste0(colnames(courtland_mutant)[1:21])
colnames(e) <- toName
pd <- data.frame(toName,
row.names=colnames(e))
pd <- new("AnnotatedDataFrame", pd)
## feature data
fd <- rownames(e)
fd <- as.data.frame(csv[,1:8])
fd
rownames(fd) <- rownames(e)
fd <- new("AnnotatedDataFrame", fd)
process <- new("MSnProcess",
processing=c(
paste("Loaded on ",date(),".",sep=""),
paste("")),
normalised=FALSE)
courtland_mutant <- new("MSnSet",
exprs = e,
phenoData = pd,
experimentData = experiment,
featureData = fd)
## summarise to protein level
courtland_mutant <- combineFeatures(courtland_mutant, method = "median", fcol = "Accession", na.rm = TRUE)
courtland_mutant <- MSnbase::normalise(courtland_mutant, method = "sum")
fData(courtland_mutant)$markers <- "unknown"
save(courtland_control, file="../../data/courtland_control.rda",
compress = "xz", compression_level = 9)
save(courtland_mutant, file="../../data/courtland_mutant.rda",
compress = "xz", compression_level = 9)
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