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Lior Pachter Profile picture
Lior Pachter
@lpachter
Bren Professor of Computational Biology @caltech. Blog at https://t.co/FFQzhEsmhi. Tweets represent my views, not my employer's. #methodsmatter
Fei Zhao Profile picture Tim Herpelinck Profile picture 3 subscribed
Apr 14 • 19 tweets • 7 min read
It's been great to see the positive response of @satijalab & @fabian_theis to our preprint on Seurat & Scanpy, and their commitment to work to improve transparency of their tools. One immediate benefit will be better practice of PCA in genomics. 1/🧵biorxiv.org/content/10.110… PCA became a mainstay in genomics after the papers of @soumya_boston, Josh Stuart & @Rbaltman () and @OrlyAlter () ca. 2000 demonstrated its power for studying gene expression. 2/worldscientific.com/doi/abs/10.114…
pnas.org/doi/10.1073/pn…
Apr 7 • 15 tweets • 7 min read
The difference in @10xGenomics' Cell Ranger's default between version 6 and 7 is discussed in this thread, but it's such a big deal that it's worth its own thread.

tl;dr: in v7 Cell Ranger changed how it produces the gene count matrix leading to a huge difference in results. 1/ The change was described in release notes on May 17, 2022, which via two clicks lead to a technical note with more detail: 2/ cdn.10xgenomics.com/image/upload/v…
Image
Apr 5 • 25 tweets • 10 min read
The choice of whether to use Seurat or Scanpy for single-cell RNA-seq analysis typically comes down to a preference of R vs. Python. But do they produce the same results? In w/ @Josephmrich et al. we take a close look. The results are 👀 1/🧵 biorxiv.org/content/10.110…
Image We looked at a standard processing / analysis summarized in the figure below. The sources of variability we explored are in red. The plots and metrics we assessed are in blue. We examined the standard benchmark 10x PBMC datasets, but results can be obtained for other data. 2/ Image
Feb 21 • 24 tweets • 8 min read
My blog passed 3 million views today from more than 1.8 million visitors. There have been a total of 119 posts in just over 10 years.
I'm one of those visitors. The blog is an idea repository and I go back sometimes for recall. Some highlights 1/🧵 liorpachter.wordpress.com
Image Just today I revisited the PCA post to recall some of the properties of the transform. A student, Nick Markarian, taught me the Borel-Kolmogorov paradox today (topic for a future post) and the post was helpful in thinking about some things. 2/ liorpachter.wordpress.com/2014/05/26/wha…
Dec 24, 2023 • 51 tweets • 20 min read
This year I had the privilege of enjoying in-person conferences again, and in April I met @dvir_a & Dan Gorbonos, from whom I learned a bunch of interesting science. Here we are having burgers at Hans im Glück in Bonn.
And now, a 🧵about genocide.. 1/ The topic came up at dinner. History presents a heavy burden for Jews in Bonn.. even 78 years after WWII. The "Hans in luck" restaurant we were dining at is just a few meters from where the local synagogue was burned down during "Kirstallnacht" in 1938. 2/ Image
Dec 12, 2023 • 15 tweets • 6 min read
🌌The virial theorem relates time-averaged kinetic energy of objects to their potential energy.

🧬The Price equation relates change in a trait over time in subpopulations to their fitness.

In we observe that the virial theorem is the Price equation. 1/🧵arxiv.org/abs/2312.06114 The virial theorem is a 150-year old tool in (astro)physics. First described by Rudolf Clausius in 1870 in connection with studies of heat transfer, it gained prominence after it was used by Fred Zwicky in 1933 to posit the existence of dark matter. 2/
Dec 11, 2023 • 25 tweets • 8 min read
This speech by @FareedZakaria is a litany of misinformation. There is much to improve at US universities, but his claims are false and unhelpful.

A rebuttal: 1/🧵 The speech begins with the claim that the public has been losing faith in universities because universities are pushing political agendas instead of catering to excellence. But he provides no evidence of a link.

Hypothesis: the main factor is cost. 2/
foxbusiness.com/economy/colleg…
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Aug 23, 2023 • 27 tweets • 9 min read
A 🧵 on why Seurat and Scanpy's log fold change calculations are discordant. 1/

(based on the Supplementary Notes from ). biorxiv.org/content/10.110…

Image I first became aware of the discrepancy in LFC reporting by Seurat and Scanpy from a preprint by @jeffreypullin and @davisjmcc:

The result seemed surprising because it didn't seem like calculating log(x/y) = log(x)-log(y) should be complicated. 2/
May 2, 2023 • 6 tweets • 3 min read
Actually, not transforming the data outperforms log(y/s+1). 1/ The "performance" in this analysis boils down to checking consistency of the kNN graph after transformation. That's certainly a property one can optimize for, but it's by no means the only one. In fact, if it was the only property of interest, one could just not transform. 2/
May 2, 2023 • 17 tweets • 6 min read
In a recent preprint with @GorinGennady (biorxiv.org/content/10.110…) we provide a quantitative answer to to this question, namely what information about variance (among cells in a cell type, or more generally many cell types) does a UMAP provide? A short🧵1/ The variability in gene expression across cells can be attributed to biological stochasticity and technical noise. In practice it's hard to break down the variance into these constituent parts. How do we know what is biological vs. technical? 2/
May 2, 2023 • 21 tweets • 10 min read
In 2019 "Single-cell multimodal omics" was deemed @naturemethods Method of the Year, and since then many new multimodal methods have been published. But are there tradeoffs w/ multimodal omics?

tl;dr yes! An analysis w/ @sinabooeshaghi & Fan Gao in biorxiv.org/content/10.110… 🧵1/ There are a lot of ways to look at this question and we have much to say (long 🧵ahead!). As a starting point let's begin with our Supplementary Figure 4. This is a comparison of (#snRNAseq+#snATACseq) multimodal technology with unimodal technology. Much to explain here: 2/ Image
Mar 23, 2023 • 16 tweets • 6 min read
To follow up on this comment by @nilshomer, I wanted to say a few things about why @sinabooeshaghi designed and developed seqspec (just pre-printed here biorxiv.org/content/10.110…), and our hopes for how it can be used for transparency and reproducibility in genomics. 🧵1/ Since the development of sequence census assays by Barbara Wold in her pair of transformative papers in 2007--2008 on Chip-seq and RNA-seq (science.org/doi/10.1126/sc… and nature.com/articles/nmeth…), the use of sequencing for molecular biology has exploded. 2/
Jan 19, 2023 • 23 tweets • 13 min read
Interested in "integrating" multimodal #scRNAseq data? W/ @MariaCarilli, @GorinGennady, @funion10 & Tara Chari we introduce biVI, which combines the scVI variational autoencoder with biophysically motivated bivariate models for RNA distributions. 🧵 1/
biorxiv.org/content/10.110… One of the clearest cases for "integration" is in combining measurements of nascent and mature mRNAs, which can be obtained with every #scRNAseq experiment. Should "intronic counts" be added to "exonic counts"? Or is it better to pick one or the other? 2/
Jan 2, 2023 • 27 tweets • 8 min read
This flippant comment on #scRNAseq algorithms reflects a common disrespect for computational biologists who are frequently derided for not asking "good biological questions". Moreover, it is peak chutzpah. A short 🧵.. As pointed out by @RArgelaguet, the OP recently coauthored a paper where many #scRNAseq methods, algorithms, and tools were used.. I wonder which of them the OP would have preferred was not developed. @AMartinezArias, please choose from this list:
Dec 22, 2022 • 9 tweets • 4 min read
You have to hand it to Lex Fridman. His grift is not an amateur job. Take his Twitter photo. A professor standing in front of a blackboard with some math. Right? This photo (see RHS of image below) is from what he calls his "MIT course" on Deep Learning for Self-Driving Cars. Sounds like good stuff. CS, math, self driving cars. #broheaven. So what is the problem? He is standing in front of the blackboard.
Dec 20, 2022 • 5 tweets • 2 min read
One of the Christmas stories that's almost completely forgotten is that of Bogdanovka. Starting on Dec. 21, 1941, tens of thousands of Jews were murdered in a camp in what is present day Ukraine by Romanian soldiers, ethnic Germans & Ukrainian police. 1/5

timesofisrael.com/romanias-homeg… Large groups of hundreds of Jews were marched to a ravine in a forest and shot. Those who couldn't manage the march were murdered by the thousands in pigsties in which they were locked that were set on fire. Many others froze to death. degruyter.com/document/doi/1… 2/5
Dec 19, 2022 • 13 tweets • 5 min read
So I got an email from a place called RayTech Group offering me $10,000 per month to write recommendation letters for their students who "need apply universities" with the stipulation that "the content of the recommendation letters can be further discussed" with me. Their website (raytech.group) says that they achieve "students' comprehensive 'background development'" and "enhance the competitiveness of students at school age. As soon as possible to achieve the Offer from famous universities and enterprises."
Dec 4, 2022 • 16 tweets • 10 min read
In a new preprint w/@kreldjarn, @DelaneyKSull, @GuillaumOleSan & @pmelsted we address a shortcoming in current approaches to quantifying single-nucleus RNA-seq: biorxiv.org/content/10.110…
tl;dr care has to be taken in quantifying nascent vs. mature transcripts. #snRNAseq #scRNAseq🧵 First, note that single-cell RNA-seq data provides some quantification not only of processed (mature) messenger RNAs, but also of nascent molecules. That observation by @GioeleLaManno, @slinnarsson and colleagues underlies RNA velocity. But what about single-nucleus RNA-seq? 2/
Nov 18, 2022 • 5 tweets • 3 min read
The "genius" @elonmusk was a year ahead of me @PtaBoysHigh. Every year they gave awards to those "worthy of praise" (digni laude). Perhaps it's not a big surprise that Musk was never deemed "worthy of praise". Which is fine, of course. Awards like this are rubbish anyway. But friendships aren't, and the people I miss from school, and there are many... are not Musk (in this photo he is front row left).
Nov 11, 2022 • 6 tweets • 1 min read
Why are they selling poppies, Mummy?
Selling poppies in town today.
The poppies, child, are flowers of love.
For the men who marched away. But why have they chosen a poppy, Mummy?
Why not a beautiful rose?
Because my child, men fought and died
In the fields where the poppies grow.
Oct 29, 2022 • 19 tweets • 6 min read
This is rubbish. Shame on @sapinker for spreading this misogyny. A 🧵... Let's start with the article he links to. It begins w/ "Women are now 60 percent of college graduates, men a mere 40 percent" describing this as "the fading male presence". Bollocks. The percentage of males who have completed four years of college has soared: 6% to 37% in 80 yrs.