Unbiased spatial proteomics with single-cell resolution in tissues

Mund, Andreas; Brunner, Andreas-David; Mann, Matthias

doi:10.1016/j.molcel.2022.05.022

Cited by 99 publications

(71 citation statements)

References 105 publications

(139 reference statements)

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“…Recent progress in mass spectrometry instrumentation and data processing methods has led to a rapidly increasing interest in novel technologies and applications that involve proteomic profiling of ultra-low peptide amounts. These facilitate, for example, single-cell proteomics or spatial proteomic profiling of tissues, which can offer unique biological and biomedical insights [13][14][15][16][17][18][26][27][28][29] . Still, so far these methods have inevitably required peptide separation using nanoflow gradients to achieve the required sensitivity, including, in some cases, flow rates below 100 nl/min.…”

Section: Slice-pasef Facilitates High-throughput Microflow Analysis O...mentioning

confidence: 99%

“…Large-scale proteomic screens for systems biology experiments and biomarker discovery in patient cohorts are now streamlined [3][4][5][6][7][8][9][10][11][12] . Furthermore, recent high-sensitivity applications, such as single-cell proteomics and spatial tissue proteomics, have been rapidly gaining traction in the field [13][14][15][16][17][18] . High sensitivity applications in proteomics are currently hampered by two key limitations.…”

Section: Introductionmentioning

confidence: 99%

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Slice-PASEF: fragmenting all ions for maximum sensitivity in proteomics

Szyrwiel

Sinn

Ralser

et al. 2022

Preprint

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We present Slice-PASEF, a novel mass spectrometry technology based on trapped ion mobility separation of ions. Slice-PASEF allows to achieve the theoretical maximum of MS/MS sensitivity and boosts proteomics of low sample amounts. Leveraging Slice-PASEF, we show, for the first time, that comprehensive profiling of single cell-level peptide amounts is possible using ultra-fast microflow chromatography and a general-purpose mass spectrometer, allowing quantification of 1417 proteins from 200 picograms of a HeLa cell peptide standard on an Evosep One LC system coupled to a timsTOF Pro 2, at a 200 samples per day throughput. We implemented a Slice-PASEF module in our DIA-NN data processing software, to make it readily available for the proteomics community.

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Section: Slice-pasef Facilitates High-throughput Microflow Analysis O...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Slice-PASEF: fragmenting all ions for maximum sensitivity in proteomics

Szyrwiel

Sinn

Ralser

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Mapping the profiling data to the ROIs can provide vital information about the tumour and TME. Major advances in mass spectrometry hardware now enable deep profiling capabilities at the single-cell level [ 102 , 103 ]. Use of artificial intelligence to integrate high-resolution imaging data to ‘omics’ datasets (including transcriptomics) would provide an ideal function-based snapshot of the biospecimen.…”

Section: Future Directionmentioning

confidence: 99%

Crosstalk between Immune Checkpoint Modulators, Metabolic Reprogramming and Cellular Plasticity in Triple-Negative Breast Cancer

et al. 2022

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Breast cancer is one of the major causes of mortality in women worldwide. Accounting for 15–20% of all breast cancer diagnoses, the triple-negative breast cancer (TNBC) subtype presents with an aggressive clinical course, heightened metastatic potential and the poorest short-term prognosis. TNBC does not respond to hormonal therapy, only partially responds to radio- and chemotherapy, and has limited targeted therapy options, thus underlining the critical need for better therapeutic treatments. Although immunotherapy based on immune checkpoint inhibition is emerging as a promising treatment option for TNBC patients, activation of cellular plasticity programs such as metabolic reprogramming (MR) and epithelial-to-mesenchymal transition (EMT) causes immunotherapy to fail. In this report, we review the role of MR and EMT in immune checkpoint dysregulation in TNBCs and specifically shed light on development of novel combination treatment modalities for this challenging disease. We highlight the clinical relevance of crosstalk between MR, EMT, and immune checkpoints in TNBCs.

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“…Background Spatial biology enables the interrogation of tissue composition at a single cell level with preservation of spatial context, which opens new avenues for tumor microenvironment (TME) studies. 1 Biomarkers' composition of the tissue can be interrogated with hyperplexed immunofluorescence, wherein an imaging detection is performed for each marker on the same slide. The COMET™ platform performs sequential immunofluorescence (seqIF ™) and enables full automation of such workflow, where: up to 40 biomarkers can be detected with full automation from staining to data acquisition.…”

mentioning

confidence: 99%