iiinova — where your digital self keeps evolving

Jeff Mold @jeffmold.bsky.social · 10/10/2026

Falls asleep with his toys too

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Jeff Mold @jeffmold.bsky.social · 09/10/2026

My border collie’s ball catching skills are fire

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Jeff Mold @jeffmold.bsky.social · 07/10/2026

I am sure I have photobombs but I quite like him when he is not being crazy and just snuggling his turtle...

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Jeff Mold @jeffmold.bsky.social · 31/08/2026

My dog buttons has some special gifts

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Jeff Mold @jeffmold.bsky.social · 28/08/2026

This little guy followed my me and my dog on our walk. I think he wants to be friends? I named him Bilbo

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Jeff Mold @jeffmold.bsky.social · 05/08/2026

Sounds like they aren’t clear it’s a covid thing. Might be worth stating that up front or looking at flu infection patients?

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Jeff Mold @jeffmold.bsky.social · 13/04/2026

This is buttons. I call this move the wiggle worm. I know he’s itching his back but when I say wiggle worm he now does this 😂. I guess I can vocally make him itchy

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Jeff Mold @jeffmold.bsky.social · 26/03/2026

I think I might be on the scoundrel list amongst purists…

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Jeff Mold @jeffmold.bsky.social · 09/03/2026

so focused here I am not sure how to explain this subtle but reproducible wavy up/down pattern in the top sample vs the bottom but it really doesn't seem technical. I figure in dividing cells you might increase copies unevenly during S phase but not sure if that looks like this?

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Jeff Mold @jeffmold.bsky.social · 09/03/2026

So this is a very messed up cell line - where there is typically 3 Chr5 - and the experiment has a pre and post-treatment on the same isogenic clonal population. The thing that puzzles me is that there is low level read depth variability both gains/losses in certain chromosomes like Chr5

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Jeff Mold @jeffmold.bsky.social · 09/03/2026

I have a question for people who have a lot of experience on CNV calling on WGS data - does seeing this pattern in 1MB binned 10x coverage WGS (just looking at read depth) present an obvious signal for anything? These are two clones of a cell line (top and bottom) and focus on Chr5 (middle)

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Jeff Mold @jeffmold.bsky.social · 22/01/2026

Similarly it is not standard (to my knowledge) to try and interpret whether having a higher fluorescence for IFNg means that the cell is better at making it compared to lower fluorescence. Usually gates are drawn and cells are determined to be capable of responding to a stimulation or not.

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Jeff Mold @jeffmold.bsky.social · 22/01/2026

This is a random image from google - but it illustrates the point. Nothing can be inferred from the level of Ki67 expression here. A low expression might indicate background staining but generally it is treated as either a dividing or non-dividing cell. Being high or medium high is irrelevant.

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Jeff Mold @jeffmold.bsky.social · 22/01/2026

So to come up with this figure (below) they first took every gene set from MSIGDB and then they filtered for ones with 'stem' in the name and at least 4 genes (which seems to be no filter because they have the same 1197 before and after). In addition they harvest signatures from selected papers.

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Jeff Mold @jeffmold.bsky.social · 22/01/2026

I have a serious question for the bioinformatics community - it is now very trendy to assign genes to modules or groups and then annotate those groups using various strategies. When I read the methods for papers it is unclear to me how one comes up with the strategy they use - see below:

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Jeff Mold @jeffmold.bsky.social · 20/01/2026

Trump keeps complaining to the Norwegian government about his lack of prizes…. “edition.cnn.com/2026/01/19/europe/t…”

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Jeff Mold @jeffmold.bsky.social · 17/01/2026

and (2) I never feel like the actual data looks all that different regardless of the statistics. The graphs don't look as if they suggest a difference really exists. In this paper www.nature.com/articles/s41... They used a BACH2 regulon score on human CAR T cells - I am perplexed at the p-value

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

The authors write this about the human data - I think it is quite a stretch to say the data above demonstrates a role for PARP in memory T cell differentiation in humans?!? Right? Or am I a jerk :) (or both)

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

So in Ext Fig 3 they define the groups - and throughout the rest of the paper this comparison is made (Tcm vs CD44hiCD62Lhi) - wouldn't it at least be worth asking if the top percentile of untreated cells was =?

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

A lot of the results are based on gating like this - where they take cells that are all in the top quadrant (presumably all CD44+CD62L+ and then divide them into CD44hiCD62Lhi vs intermediate and calculate lots of stats based on secondary FACS data often not shown (like IFNg, Ki67 etc..)

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

There is a bit of human data here and I would first like to comment on that - these are from ovarian cancer patients samples pre and post PARP treatment. It is a strange result for a few reasons I will go through: (1) why use CD62L MFI on cells already gated as CD45RO+CCR7+ and what is that axis?

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

In fact I would interpret the three subclusters of cells they see as basically roughly equivalent barring some extra protein based measurements which were more clear than the scRNA data. It clear in the bottom figure where we are looking at mostly high expressed genes with relative differences

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Jeff Mold @jeffmold.bsky.social · 13/01/2026

The idea of a novel 'GZMA+KLF2+' vs 'GZMA+KLRG1+' population of T cells is not really borne out of the data - Based on the dotplot the vast majority of cells are KLF2+ and there MIGHT be differences in expression levels between some populations but hard to say if it is meaningful.

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Jeff Mold @jeffmold.bsky.social · 09/01/2026

100% Border Collies - ok now it makes sense.

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Jeff Mold @jeffmold.bsky.social · 09/01/2026

I am trying to figure out the breed of the gifted dogs - it looks like they are Border Collies from the cartoons, at least the controls are Border Collies. This passage from Ref24 of the paper stands out - If you enter your dog in a Scientific study please name it something like 'Pickles'...

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Jeff Mold @jeffmold.bsky.social · 09/01/2026

I wasn't aware they were looking? Sounds like a George Church venture.

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Jeff Mold @jeffmold.bsky.social · 16/12/2025

I know this one! It’s great. I’d say that there’s a decent amount of IgG though and I wonder how many PCs you need to inflict major damage in a tissue given how few are needed in BM to afford humoral immunity?

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Jeff Mold @jeffmold.bsky.social · 11/12/2025

Oh no... we have a new 'single cell RNAseq reveals...'

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Jeff Mold @jeffmold.bsky.social · 09/12/2025

Also it’s a bit of a red flag when they get a result that goes against their hypothesis and they try to hand wave it away…

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Jeff Mold @jeffmold.bsky.social · 03/12/2025

Just 8 months ago he was heart breakingly cute

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Jeff Mold @jeffmold.bsky.social · 03/12/2025

I just wanna brag about what a beautiful little puppy I have :)

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Jeff Mold @jeffmold.bsky.social · 03/12/2025

I just wanna brag about what a beautiful little puppy I have :)

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Jeff Mold @jeffmold.bsky.social · 03/12/2025

I have been trying to figure out what to take away from the CD8 T cell data in the different papers - since this one (www.nature.com/articles/s41...) has clonotype information I focused on it - am I accurate in reading that CD8 T cells expanded against HIV epitopes are made of 2-5 clones only?

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Jeff Mold @jeffmold.bsky.social · 13/11/2025

www.science.org/doi/10.1126/... Buttons approves of this work

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Jeff Mold @jeffmold.bsky.social · 06/11/2025

In fact if you exclude the Tregs there are precious few cells in this dataset relative to adults that are classified as non-naive looking? Am I missing something?

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Jeff Mold @jeffmold.bsky.social · 06/11/2025

Why don’t they just call them Tregs as we and others described 15-20 years ago?!

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Jeff Mold @jeffmold.bsky.social · 03/11/2025

About five years ago I wrote on Twitter that it feels like there was bimodal income distribution in the USA and got slammed and ridiculed by academic economists -

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Jeff Mold @jeffmold.bsky.social · 30/10/2025

Wow this is quite a statement:

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Jeff Mold @jeffmold.bsky.social · 23/10/2025

Nature... you belittle yourself. Next time just go for the '10 reasons why the COVID vaccine might cure your cancer - you won't believe number 7!'

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Jeff Mold @jeffmold.bsky.social · 24/09/2025

Don’t do a bad thing because later it might be done to you is a first grader level of moral thinking fyi

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Jeff Mold @jeffmold.bsky.social · 06/09/2025

And this justification re: stats.

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Jeff Mold @jeffmold.bsky.social · 07/08/2025

Me too but now I’m wondering if they aren’t macrophages…. The same Ab stains the prostate like this:

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Jeff Mold @jeffmold.bsky.social · 02/08/2025

What sorts of largeish cells live in between the semineferous tubules at about 1-10% frequency like this:

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Jeff Mold @jeffmold.bsky.social · 26/07/2025

For example see the overview of the data: what is the odd population only seen in fetal cd4?! (My guess fetal tregs). And there’s barely any signs of effectors/memory

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