It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Multi-omics profiling by CITE-seq bridges the RNA-protein gap in single-cell analysis but has been largely applied to liquid biopsies. Applying CITE-seq to clinically relevant solid biopsies to characterize healthy tissue and the tumor microenvironment is an essential next step in single-cell translational studies. In this study, gating of cell populations based on their transcriptome signatures for use in cell type-specific ridge plots allowed identification of positive antibody signals and setting of manual thresholds. Next, we compare five skin dissociation protocols by taking into account dissociation efficiency, captured cell type heterogeneity and recovered surface proteome. To assess the effect of enzymatic digestion on transcriptome and epitope expression in immune cell populations, we analyze peripheral blood mononuclear cells (PBMCs) with and without dissociation. To further assess the RNA-protein gap, RNA-protein we perform codetection and correlation analyses on thresholded protein values. Finally, in a proof-of-concept study, using protein abundance analysis on selected surface markers in a cohort of healthy skin, primary, and metastatic melanoma we identify CD56 surface marker expression on metastatic melanoma cells, which was further confirmed by multiplex immunohistochemistry. This work provides practical guidelines for processing and analysis of clinically relevant solid tissue biopsies for biomarker discovery.
CITE-seq analysis in healthy skin, and both primary vs. metastatic melanoma samples suggests practical considerations of different skin dissociation protocols and dynamic thresholding of antibody signals for biomarker discovery.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details







1 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642)
2 Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland (GRID:grid.7400.3) (ISNI:0000 0004 1937 0650)
3 ETH Zurich, NEXUS Personalized Health Technologies, Schlieren, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); SIB Swiss Institute of Bioinformatics, Zurich, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006)
4 Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780)