Prioritized single-cell proteomics

While the sensitivity of mass spectrometry (MS) is often cited as a major limitation for single-cell proteomics, current methods can detect over 60 000 peptide-like features from individual cells analyzed by label-free MS. Yet, because of time constraints, shotgun methods can perform MS2 scans on only a fraction of all detected peptide-like features and identify the amino acid sequences of even a...

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Single-cell proteomics: Reviews & perspectives

Early experimental investigations of cellular heterogeneity used methods based on fluorescent proteins and antibodies, and these methods have been widely used for single-cell protein analysis over the last couple of decades. They have contributed to many foundational results discussed in this review. However, these methods limit both the number of proteins that can be analyzed and the specificity of the analysis. Furthermore, these methods are limited in their ability to quantify similar proteoforms. These limitations may be overcome by...

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Research success

There can be many definitions of successful research and many factors that contribute to it. Comprehensively discussing all of these can fill the pages of several books and is beyond the aims of this post. Rather, I want to focus on two factors that I consider most important for success as I define it: Accelerating the rate of progress. Making discoveries that stand out and stand the...

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When do you need single-cell analysis?

Single-cell analysis is trendy for good reasons: It has enabled asking and answering important questions. Of course, the substantive reasons are surrounded by much hype. Sometimes colleagues tell me they want to add single-cell RNA-seq analysis since it will help them publish their paper in a more prestigious journal, and sadly there is perhaps more truth to that than I want to believe.

On the other end of the spectrum, some colleagues from the mass-spec community are puzzled by our efforts to develop methods for ...

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Direct causal mechanisms

Understanding biological systems: In search of direct causal mechanisms

The advent of DNA-microarrays spurred a vigorous effort to reverse engineer biological networks. Recently, these efforts have been reinvigorated by the availability of RNA-seq data from perturbed and unperturbed single cells. In the talk below, I discuss the opportunities and limitations of using such data for inferring networks of direct causal interactions, with emphasis...

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Single-cell proteomics


Ever since my lab posted the SCoPE-MS preprint, I have been repeatedly asked about the future potential and the cost of quantifying proteins by high-throughput mass-spectrometry in single cells. I will summarize a few thoughts that hopefully will be helpful and will reduce email traffic.

Why quantify proteins and PTMs in single cells?

Single-cell RNA-seq has made great strides and become widely available and preferred method for high-throughput single-cell measurements. That is great! These...

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