Lior Pachter Profile picture
Bren Professor of Computational Biology @caltech. Blog at https://t.co/FFQzhEsmhi. Tweets represent my views, not my employer's. #methodsmatter
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Sep 10 11 tweets 5 min read
So this plagiarism thing has happened to our lab.. again. This time it's plagiarism of our poseidon syringe pump paper @booeshaghi et al., 2019 in @SciReports:
Text has been plagiarized, as well as figures copied directly here: 1/🧵nature.com/articles/s4159…
ijirset.com/upload/2024/ma… Here is figure 1 from our paper (LHS) and figure 1 in the plagiarized paper (RHS) published in the "International Journal of Innovative Research" 2/ ijirset.com/upload/2024/ma…

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Aug 16 17 tweets 7 min read
I've checked this paper out, as instructed. I was also interested in the main result for personal reasons: I'm 51 years old. Is it true that I've just gone through a major change? And that another one awaits me in just a few years?

Some comments on the paper in this thread 1/🧵 The main result about major changes in the mid 40s and 60s is shown in this plot (Fig. 4a). First, I redrew it with axes that start at 0, so the scale of change here was clearer. Not as impressive, but maybe it's a thing? 2/
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Aug 10 25 tweets 10 min read
I recently posted on @bound_to_love's work quantifying long-read RNA-seq. In response, a scientist acting in bad faith (Rob Patro @nomad421) trashed our work. This kind of mold in science's bathroom is extremely damaging so here's a bit of bleach. 1/🧵 At issue are benchmarking results we performed comparing our tool, lr-kallisto, to other programs including Patro's Oarfish. Shortly after we posted our preprint Patro started subtweeting our work, claiming we'd run an "appallingly wrong benchmark" and that we're "bullies". 2/
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Aug 1 6 tweets 2 min read
This recently published figure by @Sarah_E_Ancheta et al. is very disturbing and should lead to some deep introspection in the single-cell genomics community (I doubt it will).

It demonstrates complete disagreement among 5 widely used "RNA velocity" methods 1/ Image This is of course no surprise. In "RNA velocity unraveled" by @GorinGennady et al. in @PLOSCompBiol we wrote 55 page paper explaining the many ways in which RNA velocity makes no sense. 2/ journals.plos.org/ploscompbiol/a…
Jul 29 13 tweets 4 min read
I was recently schooled on some Gen Z and Gen Alpha brainrot. Here's a yap about it:

1/🧵 Delulu:

"I just submitted my R01. I'm sure this one is going to finally get funded!"

You're delulu.

2/
Jul 25 22 tweets 7 min read
Challenge accepted. Here are a few comments on the paper after starting to wade through its massive content. The paper in question is 1/🧵 nature.com/articles/s4158…
First, the claim that "lower OPC fraction across regions and, in particular, in non-neocortex regions was significantly associated with impaired cognition (Supplementary Fig. 37d)" is not true. Supp. Fig. 37d is below. I've boxed in red the panel the claim is based on. 2/ Image
Jul 20 19 tweets 6 min read
The mantra that spatial transcriptomics is about location, location, location is catchy, but what does it really mean? We have just posted , work of Kayla Jackson et al., that describes the concordex method for identifying spatial homogeneous regions. 1/🧵biorxiv.org/content/10.110… For years there's been a notion that spatial transcriptomics should allow for the definition of "spatial regions" or "tissue domains". In quotes because they're typically defined as "whatever the algorithm outputs". E.g. GASTON "spatial domains" vs. BANKSY "tissue domains". 2/
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Jul 2 24 tweets 8 min read
Aristotle was the first to notice honeybees dancing. In 1927 Karl von Frisch decoded the waggle. How it works was "explained" by MV Srinivasan AM FRS in the 1990s. Except @NeuroLuebbert found his papers are junk. A 🧵 about her discovery & our report: 1/arxiv.org/abs/2405.12998 First, if you're not familiar with the waggle, it's Nature magic! Watch this video for cool footage and an introduction.
Aristotle's observations in Historia animalium IX are arguably one of the first instances of observation driven inquiry and science. 2/
Jun 27 12 tweets 4 min read
A lot of bioinformatics requires editing sequencing reads to facilitate QC and make them suitable for processing. To help with such tasks, @DelaneyKSull developed splitcode, now published at 1/ academic.oup.com/bioinformatics…
Image The input to splitcode are reads in FASTQ, along with a config file. The output can include edited reads or extracted subsequences, in FASTQ (including gzipped), BAM, or interleaved sequences to stdout. Regions can be identified using absolute location or relative anchors. 2/ Image
May 6 9 tweets 4 min read
For the second day of the week of observance of the Days of Remembrance of the Victims of the Holocaust a 🧵 about Sosúa.

Sosúa is a small beach town in the Dominican Republic that was founded by Jews fleeing Nazis in Europe in 1940. 1/ Sosúa is a beautiful place in Puerto Plata on the north coast of the Dominican Republic. About 56,000 people live there now.

But Dominican Republic? How did Jews end up founding a beach town in the Dominican Republic? How many Jews?

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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…
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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