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Jan 26 • 9 tweets • 3 min read
Yeah, well, it turns out grandma figured out all of the analysis methods for single-cell RNA-seq. 1/
Grandma figured out pseudotime. 2/ academic.oup.com/bioinformatics…
Grandma figured out that there is interesting geometry underlying gene expression. 3/
academic.oup.com/bioinformatics…
Grandma figured out RNA velocity. 4/
embopress.org/doi/full/10.10…
Grandma figured out how to pre-process single-cell RNA-seq. 5/
academic.oup.com/nar/article/34…
Grandma figured out how to normalize single-cell RNA-seq. 6/ academic.oup.com/biostatistics/…
Grandma figured out how to cluster cells. 7/
pnas.org/content/95/25/…
Grandma figured out a lot of other stuff too... but since nobody is listening she is going to go to bed. Maybe she'll even read a book before turning off the light.

P.S. She's she's seen the UMAP videos that grandpa is addicted to watching on TikTok and she is not impressed. 🛌
P.P.S Grandma also figured out that it's very useful to perform SVD on gene expression matrices. pnas.org/content/97/18/…

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More from @lpachter

Lior Pachter Profile picture
Jan 22
Is a single-cell RNA-seq atlas really an atlas? A short thread about #scRNAseq, maps, and atlantes (yes, the plural of atlas is atlantes! h/t @NeuroLuebbert). 🧵1/
Atlantes must be accurate to be useful, and the vexing question for centuries, namely how to best represent the spherical earth in 2D, is nontrivial. There have been many proposals with pros & cons for each (because the sphere and the plane have different Gaussian curvatures). 2/
In #scRNAseq, atlases of cells have become synonyms with UMAP figures of gene expression matrices (used to be t-SNE but UMAP seems more popular now). Map making from gene expression matrices is more challenging than map making of our 3D world; #scRNAseq is in ~10⁴ dimensions. 3/
Read 26 tweets
Lior Pachter Profile picture
Jan 22
Grigory Pereleman was making less than $100/month while working on the solution of the Poincaré conjecture at the Steklov Institute. He won't live forever, but his ideas will.
newyorker.com/magazine/2006/…
His critiques of mathematicians hold true for scientists more generally: "...there are many mathematicians who are more or less honest. But almost all of them are conformists. They are more or less honest, but they tolerate those who are not honest."
The @NewYorker piece is filled with good quotes and anecdotes that many could learn from.

"Speed means nothing. Math doesn’t depend on speed. It is about deep." - Yuri Burago. This is so so true, and not just for math.
Read 7 tweets
Lior Pachter Profile picture
Oct 7, 2021
The 17 #BICCN @nature papers on the primary motor cortex in mouse (+some human & marmoset) that were published yesterday are a major step forward in terms of open science for an @NIH consortium. For reference, links to the open access papers are here: nature.com/collections/ci… 1/🧵
First, the #BICCN required preprints of all the papers to be posted on @biorxivpreprint, and as a result the papers were already online 1-1.5 years ago. Of course the final versions now published have been revised in response to peer review. 2/
Speaking of peer review, almost all the papers were published along with the reviews. In combination with the preprints, this provides an unprecedented view of how consortium work is reviewed and how authors respond. Real data for this perennial debate: 3/
Read 17 tweets
Lior Pachter Profile picture
Sep 29, 2021
This tweet hit a nerve. 1/
In 2008, as a new professor of molecular and cell biology @UCBerkeley I presented at a seminar series intended to introduce 1st year students to research in the department. Two profs. presented each time, with food beforehand. I was paired with Thai food and Peter Duesberg. 2/
I knew of Peter Duesberg and his HIV/AIDS denialism, but I hadn't realized that he worked @UCBerkeley. We were now colleagues in the same department. 😱 3/
Read 14 tweets
Lior Pachter Profile picture
Sep 24, 2021
I like the reproducibility standards for machine learning in the life sciences by @autobencoder, @michaelhoffman, @markowetzlab, @suinleelab, @GreeneScientist & @stephaniehicks but I propose an additional platinum standard for one click reproducibility.1/
By "one click", I mean that the entire analysis be reproducible in a (free) interactive online session of @colab (or other similar service). All steps of the analysis, from downloading data to generating figures are then not only automated but accessible for users. 2/
For an example of what this entails and facilitates, see: pachterlab.github.io/CWGFLHGCCHAP_2… 3/
Read 7 tweets
Lior Pachter Profile picture
Sep 22, 2021
In response to questions & comments by @hippopedoid, @adamgayoso, @akshaykagrawal et al. on "The Specious Art of Single-Cell Genomics", Tara Chari & I have posted an update with some new results. Tl;dr: definitely time to stop making t-SNE & UMAP plots.🧵biorxiv.org/content/10.110…
In a previous thread I talked about the (von Neumann) elephant in the dimension reduction room: t-SNE & UMAP don't preserve local or global structure, they distort distances, and they are arbitrary. Almost everybody knows this but they are used anyway...
There were some interesting technical questions about our work. One question was the extent to which PCA pre-conditioning affects results. We examined this (Supp. Fig. 3). Tl;dr: it's time to stop making t-SNE & UMAP plots (with or without PCA pre-conditioning).
Read 20 tweets

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