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slavov-n.bsky.social
Mentor, scientist & engineer. Having fun in @slavovlab.bsky.social and Parallel Squared Technology Institute @parallelsq.bsky.social with biology & single-cell proteomics. https://nikolai.slavovlab.net
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We aim to create a meeting venue for interactive discussions among scientists who rarely attend the same meetings. It stimulates creativity & new research directions.

The program for the 8th single-cell proteomics conference #SCP2025 is up ! Starting in a couple of weeks: single-cell.net/proteomics/s...

I have read books on the rise of tyrannical demagogues, but I never understood the motivation of their obsequious followers, the people implementing unjustifiable whims and offering silly justifications. What motivates these people ?

Yesterday, members of @slavovlab.bsky.social were bursting with excitement for the progress they have seen since starting their PhD. Sensitivity is up ~ 1,000-fold. Throughput is up ~ 10-fold. So, I highlighted drivers of this progress: blog.slavovlab.net/2025/05/10/w... 1/2

Gene regulatory interactions are assumed to be finely tuned. Yet, making (strong) promoters from random DNA sequences is remarkably easy ! De novo evolved promoters in E. coli exhibit low noise by default. 1/2

Phosphorylation depends both on the sequence and on spatial proximity in vivo between kinases and their substrates. Both of these factors are accounted for in this preprint 1/2

Single-cell proteomics is gaining momentum. It can analyze the proteomes of ~ 1,000 single cells / day, and we need to ensure high quality cell isolation and sample preparation: ⬛️ These approaches can help: nature.com/articles/s41...

We want both scale and quality. In just a few days, we can analyze thousands of cells from complex tissues. It's important to select them well and thus minimize artifacts, such as protein leakage. www.nature.com/articles/s41...

An alternative to tSNE & UMAP for more accurate data visualization: Tree representations for distortion-free visualization and exploratory analysis of single-cell omics data. The trees are constructed to accurately represent true distances between the objects in the high-dimensional space.

To be more accessible, #SCP2025 will offer a remote broadcast. Attending virtually is free but requires registration: single-cell.net/proteomics/s...

One way for AI to exceed human performance.

This project started with an exciting discovery. As @andrewleduc.bsky.social and team interrogated deeper, we found artifactual contributions. So, we developed methods (scp.slavovlab.net/QuantQC) to reduce such artifacts. nature.com/articles/s41... rdcu.be/ekKTq 🧵

Our paper on the impact of protein leakage due to loss of membrane integrity for single cell proteomic sample prep is out in @natcomms.nature.com! We analyze thousands of primary single cells from murine tracheal tissue and record membrane permeability (sytox-green)🧵 www.nature.com/articles/s41...

A deep insight into "prompt engineering" and its connection to rubber ducking.

I tested the FutureHouse AI with some questions. Below is an example: Have CRISPR perturbations of TFs allowed confident inference of TF - target regulation? ✅ It returned relevant references ⚠️ The results offered more cheerleading than critical analysis. platform.futurehouse.org/trajectories...

AI excels at summarizing encyclopedic knowledge. For original articles, AI tends to inhibit my thoughts. It is smooth and plausibly sounding, but also shallow & mediocre. Generally, it raises the energy barrier for me to write something original that I consider good.

These papers triumphed over their rejections blog.slavovlab.net/2014/08/15/p...

Sharp questions & rigorous methods matter.

The temptation to share popular themes contributes to superficiality. Scientists are affected by this malady too. How do we promote thoughtful, critical and constructive discussions over superficial popularity.

GPT-like models trained with bio data (mostly RNA) are likely to learn correlation patterns and make useful interpolations (predictions). Since their correlative patterns reflect indirect correlations, extrapolations should be interpreted with caution.

As a PhD student, I accepted -- without much thought -- that mRNA abundance is called 'gene expression'. I used this sloppy terminology in my research articles, e.g. molbiolcell.org/doi/full/10.... Now it feels strange. Why use a vague phrase when a precise one is available ?

One of my earliest memories is of my mother telling me to never criticize our president. I remember being shocked. It made no sense to me. Her explanation also did not make much sense. So, I remember it as a strange thing that I could not understand for years.

Confounders are a major bottleneck to understanding biology. Interactions confounded by unobserved regulators (variables) cannot be causality inferred. Gazillion data points from the observed variables cannot compensate for unmeasured confounders. What can help ... 1/2

The inflection point that brought about modern molecular biology was a focus on simpler systems that allowed rigorous experiments & conclusions. This drove much progress for decades. In think modern biomedical research can learn from this past experience.

I am looking forward to this meeting !

Simpler models outperform GPT-style models of scRNA-seq data. Evaluation of the zero-shot performance of Geneformer and scGPT suggests that these models may face reliability challenges and be outperformed by simpler methods.

A very interesting preprint from @selbachlab.bsky.social . "Comparative analyses revealed widespread translation of alternative transcripts and uncovered proteolytic processing as a major, underappreciated source of proteome complexity." 1/2

We measured degradation rate for over 10,000 proteins from over 115,000 peptide sequences which allowed us to explore how the stability of alternative splicing products affects their abundance. We found a strong overall relationship and visualize a few compelling examples!

"76 percent of voters, and 61 percent of Republicans, said a president should not be able to ignore the Supreme Court." I do not understand why these are not 100 %. The constitution is explicit about it. www.nytimes.com/2025/04/25/u...

Academia is not about publishing papers. It’s about creating knowledge and teaching it to the world. It’s about asking big bold questions and mentioning the next generation of intellectual leaders. The difference makes a huge difference.