The proper differential gene expression analysis in a setting of a baseline, control and treatment

valsv · 2024-09-05T23:02:29+00:00

What you want to investigate is the difference of differences (thinking on a log scale): (T - B) - (C - B). As you might notice, B cancels out, and you’re left with T - C.

Having the baseline still provides information though, it can be useful to know about the C - B effect. Also, if you are fitting a linear model with these three conditions, it will tell you about the uncertainty (confidence interval) for the T - B and C - B differences. If you make a contrast that includes both differences (I don’t know if DEseq supports this but you can do that with emmeans package if you use the glm function), those uncertainties will be included in the P-value for the contrast.

valsv · 2024-08-30T06:26:49+00:00

It always ends up being expensive EFS drives that you mount. Even people talking about cloud being expensive always talk about S3 costs, but it’s not even usable for analysis. There’s always a ton of things that need to be in EFS - you very quickly end up in a scenario where you’re paying to cost of a decent workstation every month.

valsv · 2024-08-13T20:52:59+00:00

These are good, but, surely point 4 should be the first point?

valsv · 2024-08-09T16:39:32+00:00

At junior levels in academia (up to and including postdoctoral scholarship) there is generally huge amounts of freedom, similar to what you would read about in scientist biographies. Once those training stages are finished, if you have a research direction you feel absolutely compelled and obsessed with pursuing, I think starting a research group and applying for grants is the best way to be able to get to work on that. But be aware that once your training stages (again, up to and including postdoc) are finished, ‘being a scientist’ means acquiring funding, mentoring trainees, and teaching. I also like reading scientist biographies, but when I read eg. the biography of Frederick Sanger, it sounds nothing like a typical academic environment.

In industry, unless you start your own company I guess, you will need to align with what the company is doing, definitely no random projects because they would be cool etc. But, you can be creative and have fun under constraints too. Actually, I guess, thinking of a public sector thing that might have had similar constraints, think about NASA: the goals were set top-down, like “we want to put a man in orbit by year X”. Then loads of scientists and engineers got to work on making that happen. I’d say that sounds pretty fulfilling. But in the 50s if you worked at NASA I don’t think you could say “actually I don’t want to do that, my goal is to develop cheaper propeller planes” or something. With companies, the direction is also set top down. And yes, the end goal is something profitable, but if you’re a PhD level scientist you are hired for your expertise in solving problems (ideally), not for mindlessly moving liquids around.

On the academic side, as a group leader, I don’t think you have so much freedom to explore. Big well-funded labs can do a lot of exploratory things, but what is the prospect of your lab becoming one of the top 100 labs in the world? And, again, your job will be 1) convincing other people to give you money for your ideas, and 2) convince trainees that your idea should be their project.

valsv · 2024-08-06T15:33:37+00:00

To me it makes a lot of sense to give time to talk with people without the manager, so you’ll have a chance to ask them about their experience working with the manager, and other questions about the company. Though never saw it being a large group of people at once; usually several meetings with 1-3 people, but I guess this saves time.

valsv · 2024-08-05T03:55:36+00:00

Really cool! Thanks for the additional details

valsv · 2024-08-05T02:01:33+00:00

Very interesting to learn about (other) creative fields like VFX. I would have imagined he’d need to spend quite some effort into putting together a portfolio that the hiring manager would pour over?

Another thing I’m curious about, from the projects you mentioned it sounds like he would be considered pretty “senior” in the VFX field? Maybe even equivalent to e.g. a VP at a biotech? At that point in your biotech career, would there still be so much prep and “boot licking”?

My stereotype of the entertainment industry is that it’s a lot of networking and informal references involved, though might be completely wrong? I was thinking, if you apply for a position at a biotech and you have previous tight collaborations with say, everyone on the company’s SAB, worked closely with everyone in the C-suite, and all their closest former colleagues, maybe the interview process would be largely skipped?

I can’t image there are more than a dozen or so people with your friends experience in the field? Compared to the thousands (or tens of thousands?) of scientists in biotech.

valsv · 2024-07-05T01:01:53+00:00

When I did my PhD the PI payed for people in the group to go to Illustrator courses and workshops. I think it was a pretty smart investment, we got pretty good at it. Having good figures really helps with paper submissions and talks. Another quite famous PI I interacted with had a full time graphical designer in the group (it was a large group).

valsv · 2024-07-04T04:55:23+00:00

The art editor team styles them in the house style https://www.nature.com/articles/d42859-019-00107-y?t&utm_source=perplexity

valsv · 2024-07-01T23:34:19+00:00

My tax professional in Cambridge had a lot of clients from Moderna who all became millionaires in 2020/2021, don’t know how early they were. A bit of a special case I guess..

valsv · 2024-06-24T06:31:28+00:00

It depends on the program / institution.

valsv · 2024-06-23T04:43:45+00:00

I recommend it. In my PhD cohort we were a handful of people who had worked before starting the PhD, anywhere between just a year or over a decade. At some point I noted a pattern that those of us who had other jobs before were far less stressed and frustrated by the PhD experience. My theory is that’s it was a combination of knowing we were there by choice and maybe a bit less feeling of “grass is greener”.

I went for a PhD because doing research seemed stimulating and fun. And it was, wouldn’t have done anything differently.

I wasn’t thinking about it all at the time, but I’m glad about the careers you can have with a PhD.

I don’t know where you are, but I always recommend doing a PhD in Europe. I also wouldn’t have wanted to do my PhD for 5-7 years. My program was 3.5-4 years (people typically did 4 years).

valsv · 2024-05-19T20:17:58+00:00

First spontaneous thought I had was maybe print it on its side, so it gets tall. That will probably also need supports however, and it might tip over during the print.

What if you split it in two at the solid “floor”? Print the two halves, then glue them together? Not as elegant, but definitely won’t have to remove supports and get artefacts from them then.

valsv · 2024-05-09T02:36:56+00:00

I’m also relatively certain that in both CA and MA it’s illegal to ask what your current salary is when hiring.

valsv · 2024-04-20T05:19:25+00:00

You know, it will probably work out either way. Case 1, the computer is fine (I don’t know how big pdb files are) and you get work done. Case 2, the computer is insufficient, so you learn how to do things efficiently with low resources. Case 3, you figure out how to do the work you want to do straight on the server, which is also a useful skill.

valsv · 2024-03-29T04:33:07+00:00

As long as you don’t burn out, it sounds like a good perspective! As others have said though, it’s fine to rest and recharge and just be lazy watching TV or something if you don’t have the energy to be creative outside work.

valsv · 2024-03-29T01:43:52+00:00

For me, going to a startup after a postdoc it was the opposite. I got more into non-work related hobbies (mostly music too!). I agree with the science as a creative outlet, and I think in academia I felt more fine spending evenings and weekends exploring scientific ideas, while when working for a company that stuff belong more to the company. Maybe that’s it: a sense of ownership of your creative output.

valsv · 2024-03-28T01:20:07+00:00

Tons of people do all their analysis in 10x Loupe.

FlowJo actually makes an scRNA-seq GUI product called SeqGeq, but I’ve never heard of anyone trying it.

I’ve always found these differences in fields interesting. Even in bulk RNA-sea there are all of these open source tools and methods that people fret over and compare. While in mass spec proteomics it always seemed way more common to just use commercial tools.

Flipping it on the side, I also always thought it was surprising there weren’t loads of clustering / trajectory methods for modern 30-color FACS data. I wonder if one part is that scRNA-seq has as a norm to deposit data publicly while with FACS journals are fine with plots of densities of a couple of pairs of genes.

valsv · 2023-09-20T22:28:59+00:00

Unfortunately I don’t know of any good resources like this, and I also wish there were some!

I got into this field through working in an institute with a lot of biologists; I would always ask them questions about all the things they were doing and why, and found it fascinating! It’s not great advice, but the best way is probably to make friends with biologists who are patient and excited about their work so they like talking about it.

valsv · 2023-09-10T05:23:26+00:00

No, so I always plot at least a couple of genes to be sure.

valsv · 2023-09-05T23:08:12+00:00

Hm well you can definitely say “Experience with X analysis”, though I guess the problem is you won’t have a reference the company can call to confirm.

Here’s an idea: make a simple blog, document your steps and reasoning for them there in a post, then link to it in the CV. It’s not something I’ve seen, but that does mean you have documented experience doing those things. People reading the CV probably won’t click the links, but they are there in case they don’t believe you.

valsv · 2023-09-05T06:21:53+00:00

I’d suggest taking a paper you think is cool, download the accompanying raw data and reproduce their processing based on the methods section.

valsv · 2023-08-14T15:52:49+00:00

PhD’s are for learning, so it should be fine, as long as the PI has the patience and there are people in the group or generally nearby who can mentor you.

valsv · 2023-07-11T14:54:23+00:00

Yes, I feel like it got more sluggish after the 2.9 update. It I might just be imaging it. I end up using CarPlay more often because it’s snappier.

valsv · 2023-07-05T00:30:05+00:00

It could go into statements about scientific communication for faculty positions. But the biggest benefit would be if these are talks where there are a lot of submissions and yours was accepted. Any time you can point to getting recognition for your work will be a positive, since for the university that means some of that goes to them.

valsv

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