Lior Pachter Profile picture
Jul 2 24 tweets 8 min read Read on X
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/
Karl von Frisch decoded the waggle, meaning he figured out how the number of waggles, and their direction, communicate information about the distance and direction of food sources. von Frisch won the Nobel Prize for his discovery. But exactly how it works remained a mystery. 3/ Image
BTW von Frisch was part Jewish, and the Nazis accused him of working with too many foreigners, too many women, and practicing "Jewish science". He was first classified as 1/8 Jewish which let him keep his post, but ultimately reclassified to 1/4.. a story for another thread.. 4/
In the 1990s, MV Srinivasan started writing papers purporting to explain the mechanisms underlying the waggle. These papers made him famous. He is a member of the Royal Society. He won the Prime Minister's Prize for Science, etc. etc. 5/en.wikipedia.org/wiki/Mandyam_V…
In 2020 @NeuroLuebbert, at the time a new PhD student, rotated in a lab where she was assigned two Srinivasan papers to present. New to the topic, she read some additional papers for context. She noticed the same data.. appearing again and again.. in different experiments. 👀 6/
In a blog post, she tells the story of the reaction she received when she pointed this out to her (tenured) professor at the time, and to others. She was basically told not to waste her time: "a lot of the scientific literature has problems". 7/liorpachter.wordpress.com/2024/07/02/the…
She tweeted out her discovery at the time. It seemed to her like a pretty big deal. It was. The response she got was basically a collective shrug. Almost no likes or retweets. 8/
But one of the responses put her in touch with @MicrobiomDigest, and led to two @PubPeer comments. See

You can guess what happened with these comments. Bupkes. 9/pubpeer.com/publications/F…
I found out about this from @NeuroLuebbert years later after she had joined my lab. To make a long story (told in the blog post ) we went back to the papers (half a dozen) and noticed many additional problems. We decided to write up her observations. 10/ liorpachter.wordpress.com/2024/07/02/the…
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What we found was very, very bad. For example, six papers reported R^2 = 0.99.. These are fits to data from experiments tracking live animals on primitive cameras in the early 2000s. 🤔 11/ Image
This is an example with reported r^2 = 0.999 for data that obviously isn't. It's from a PNAS paper
Maybe just a typo? Well no. The papers are filled with ridiculous r^2 values, and in our report we perform analyses showing they just can't all be real. 12/ pnas.org/doi/full/10.10…
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@NeuroLuebbert also found more duplications and manipulations. Crazy stuff. Identical data reported for different experiments across different papers. Some people think this kind of work, which @MicrobiomDigest does, is fun sport. It isn't. It's terribly depressing. 13/ Image
Laura was brilliant at digging through this junk. She didn't just find duplications, but also errors in key results. One is super important, a key calibration from a regression that is done incorrectly by Srinivasan et al, and inconsistent with work of others, e.g. @schuemaa. 14/
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I've mentioned MV Srinivasan several times, but we didn't set out to find errors in his work. His name was just the only one present on all the papers we found problems with. We haven't gone through his whole corpus of work 😬. 15/scholar.google.com/citations?user…
We submitted our report to @biorxivpreprint who rejected it. I get it. They didn't view it as "research", and I get where the policy comes from. But it was frustrating. Especially to be told we our manuscript contained "content with ad hominem attacks". It didn't. It doesn't. 16/
So we sent it to @J_Exp_Biol, where some of the papers were from. They rejected it as well, and asked us to individually contact all the journals. This was even more frustrating. The whole here is much greater than the sum of the parts. 17/
Eventually @J_Exp_Biol did post corrections to two of Srinivasan's papers published with them that @NeuroLuebbert had flagged. In this one Srinivasan *believes* everything is ok. 18/ journals.biologists.com/jeb/article/22…
In this one he talks about his paper *likely* containing the correct values.
Are publishers now assigning likelihood of truth?Practicing belief based science? @J_Exp_Biol's corrections here are very weak sauce. 19/journals.biologists.com/jeb/article/22…
Eventually we submitted our report to @arxiv. Although even they flagged and held it for 2 weeks, we're grateful to them for posting it. But Science has a big problem. There ought to be a place to publish critique of a body of work. Not just a complaint about one paper. 20/
That's why we titled our blog post "The Journal of Scientific Integrity". Where is this journal? Why is it so taboo to face misconduct by a scientist? People are eager to pounce on women (e.g. Claudine Gay). But I don't expect Srinivasan to be featured in the @nytimes. 21/
And yet, this is a very serious matter. I do believe that the vast majority of errors in science are innocent mistakes. But when they appear not to be, it should be ok to speak up. It should be ok to publish a critique on a body of work. 22/
Right now it's not. But it is, apparently, ok to always present "perfect" data and regressions where all the points lie exactly on a line. Srinivasan is still presenting r^2=0.99. This talk is from just a few years ago at the #ICRA18 plenary. 23/
Truth matters everywhere, but if we lose it in science, then there is meager hope elsewhere. In our abstract we conclude that "[our investigation] suggests that redoing the experiments in question is warranted." Hopefully that will happen.

Kudos to @NeuroLuebbert. 🐝 24/24

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More from @lpachter

Jun 27
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…
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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
The splitcode toolkit was motivated by our need for a versatile tool that can perform a range of tasks from adapter trimming to barcode extraction. Specialized tools exist for many tasks, e.g. fastp, UMI-tools,, etc. Splitcode is more general enabling a lot with one tool. 3/
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Read 12 tweets
May 6
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?

2/ Image
In 1938 a conference was held in Évian, France to discuss what to do about Jewish & Austrian refugees trying to flee persecution by the Nazis.

This is the same Évian of evian water. The company was founded in 1859 and was selling bottled water by 1908. But I digress.. 3/ Image
Read 9 tweets
Apr 14
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…
Back then, having linear algebra on one's side was essential. A rich lab at that time might have something like a Sun Blade workstation clocking ~500MhZ w/ 2Gb RAM. So having fast SVD algorithms made PCA practical, when other methods based on more sophisticated models weren't. 3/ Image
Read 19 tweets
Apr 7
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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To understand this technical note it is helpful to be familiar with the three types of reads that are produced in single-cell RNA-seq: spliced (M as a proxy for mature mRNAs), unspliced (N as a proxy for nascent RNAs), and ambiguous between both (labeled A). 3/ Image
Read 15 tweets
Apr 5
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…
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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
Before getting into results it's important to note that Seurat has never been published, and many of the details of Scanpy are missing in its original paper. @Josephmrich read the code & traced every function and every parameter. E.g., this is how Clustering / UMAPs are made: 3/ Image
Read 25 tweets
Feb 21
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
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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…
I've been teaching a bit of phylogenetics this year and this post on the Golden-Thompson inequality just came up. 3/liorpachter.wordpress.com/2018/10/05/rat…
Read 24 tweets

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