Proteomics

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A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts


ABSTRACT: SWATH-MS enables accurate and reproducible label-free quantification of proteomes including in extensively studied model organisms such as the mouse. Here we present a comprehensive mouse reference spectral library (MouseRefSWATH) that allows quantification of up to 10,597 proteins (62.2% of mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high protein sequence similarity between the mouse and human, facilitating the study of host microenvironment-tumour interactions from ‘bulk tumour’ measurements. We apply XenoSWATH to characterise a xenograft model of breast ductal carcinoma in-situ and uncover complex regulation of cell migration pathways that is not restricted to the tumour cells but also operates in the mouse stromal upon progression to invasive disease. MouseRefSWATH and XenoSWATH opens new possibilities for in-depth proteomic assessment to address wide-ranging biological questions involving this important model organism.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Mammary Gland Tumor Cell, Epithelial Cell, Mammary Gland

DISEASE(S): Breast Cancer

SUBMITTER: Lukas Krasny  

LAB HEAD: Paul Huang

PROVIDER: PXD017209 | Pride | 2020-06-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20190830_10wDCIS4_R1.wiff Wiff
20190830_10wDCIS4_R1.wiff.scan Wiff
20190830_10wDCIS4_R2.wiff Wiff
20190830_10wDCIS4_R2.wiff.scan Wiff
20190830_10wDCIS7_R1.wiff Wiff
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Publications

A mouse SWATH-mass spectrometry reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts.

Krasny Lukas L   Bland Philip P   Burns Jessica J   Lima Nadia Carvalho NC   Harrison Peter T PT   Pacini Laura L   Elms Mark L ML   Ning Jian J   Martinez Victor Garcia VG   Yu Yi-Ru YR   Acton Sophie E SE   Ho Ping-Chih PC   Calvo Fernando F   Swain Amanda A   Howard Beatrice A BA   Natrajan Rachael C RC   Huang Paul H PH  

Disease models & mechanisms 20200714 7


SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the chall  ...[more]

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