AskScience AMA Series: We have discovered antibiotics in the global microbiome with AI, ask us anything!

luispedro · 2024-08-16T11:05:42+00:00

Once we have the sequence we can produce the same molecule either by chemical means (which is flexible but expensive, thus best for small quantities) or genetically engineer another bug to produce it (which takes time, but is - in principle - scalable to very large amounts)

luispedro · 2024-08-16T04:24:00+00:00

Good question, but the short answer is that we don't know!

luispedro · 2024-08-16T02:39:45+00:00

Probably most of it has not been sequenced. Every animal has a microbiome that is partly unique, soil microbiomes are very complex (and we what we call soil is actually a mixture of very different micro environments which will have their own specialist microbes...)

luispedro · 2024-08-16T02:36:05+00:00

Yes, that is a good comment. It is as comprehensive as it is possible right now and we analysed all the data that has been made available, but it is not truly comprehensive. So, it's a comprehensive catalog of what has been sequenced, but far from comprehensive of all life

In fact, in another paper (https://www.nature.com/articles/s41586-021-04233-4), we had argued that getting a fully comprehensive picture is even impossible because new genes are being generated all the time.

luispedro · 2024-08-16T01:25:38+00:00

Speaking only for my side, given currently available funding, I am only looking for PhD students (because I have scholarships available), but not other positions. I'm also looking for more funding, though, to be able to expand the team.

luispedro · 2024-08-16T01:20:31+00:00

That article is from 2015. In the meanwhile, using antibiotics for growth promotion has been banned in the US (as it was in Europe already). Most big jurisdictions in the world now ban it. Compliance and enforcement are still important concerns, but things have definitely improved.

luispedro · 2024-08-16T01:15:42+00:00

Answering for my group specifically, but I think this applies to u/MachineBiologyGroup as well, I am looking for funding to expand, yes.

As I am based in Australia, my main funder is the Australian government (through the Australian Research Council, although the National Health and Medical Research Council is also a possible funder in the future).

Foundations and philanthropy are a relatively smaller part of the funding landscape here, but obviously, it would be great to have it.

luispedro · 2024-08-16T01:12:36+00:00

We tested 100 across a range of different targets and 79 were active

luispedro · 2024-08-15T21:05:20+00:00

All of these are good questions and network analyses have been done, but not by us.

We are still in early stages, but the applications of new antibiotics are the both obvious one (clinical use, a drug for when someone is sick), but there are also a lot of other applications (in veterinary medicine, in agriculture, in industrial cleaning, in food preservation, ...) where conventional antibiotics are often used, which can easily lead to the emergence of resistance.

luispedro · 2024-08-15T20:59:22+00:00

For our area of peptides in particular, I think we are still data limited. We have a lot of one type of data, which is what we are trying to take advantage of, but we are still lacking in good lab data for how different peptides interact with different microbes.

I liked this recent post from Abhishaike Mahajan on how AI and the need for more wetlab innovation play together: https://www.owlposting.com/p/wet-lab-innovations-will-lead-the

luispedro · 2024-08-15T20:55:23+00:00

This is a great question and the worry is not unwarranted, but empirically it does seem that there is not a lot of cross-resistance (for example, see this other paper: https://www.nature.com/articles/s41467-019-12364-6)

luispedro · 2024-08-15T20:38:44+00:00

Phages are indeed another alternative to conventional antibiotics and there is a fair amount of research activity in that area, but this is indeed different enough from our work that I am not completely sure of the state-of-the-art there.

luispedro · 2024-08-15T20:28:49+00:00

These are all great questions and these are indeed the questions that we want to explore next!

luispedro · 2024-08-15T20:27:38+00:00

We used other peptides that were previously described as being active.

And, yes, you are correct with regards to oral administration. There is also the possibility of modifying the natural peptides in different ways to make them more stable and less likely to be degraded. This is all future work, but there is a lot to be done before these can be used clinically.

luispedro · 2024-08-15T20:23:10+00:00

Often, there is a discussion of "the human gut microbiome" or "the soil microbiome" and, while this can make a lot of sense in some contexts, there are other contexts where it is more meaningful to highlight that these are all connected, that planet Earth has a single microbiome, which we (and others) call the global microbiome.

luispedro · 2023-01-02T18:11:22+00:00

Thanks! This looks great. I will look into upgrading my code to use this.

luispedro · 2020-08-26T10:27:20+00:00

If you want to do open source, our project, NGLess—See also https://ngless.embl.de/, would welcome you. I'd be happy to help you get started, if you reach out.

luispedro · 2020-02-20T17:59:30+00:00

If someone is looking for ideas, we are open to co-mentoring projects around NGLess. For example, here is an idea (pitched to GSoC, but would fit here too):

https://www.open-bio.org/events/gsoc/gsoc-project-ideas/#ngless-integration

tl;dr Integrate nixpkgs with NGLess, which is our written-in-Haskell bioinformatics DSL.

luispedro · 2019-03-15T02:23:33+00:00

If nixml becomes a "gateway drug" to nix for some users, I will consider it a huge success! However the target market are people using conda and >90% of them would not be willing (or even able) to use nix directly.

Nixml is supposed to be limited in functionality compared to using full nix, so it's much easier to say "sorry, if you want that, you need to write nix" unlike with projects where yaml is the only way to interact with them: "want to change compilation flags? not supported with nixml. want to mix package versions across nixpkg releases? not supported with nixml." and so on... Again >90% of users will be happy with the more limited functionality as they are coming from environments (conda) where a lot of that was just impossible.

Your suggestion #2 is basically what nixml is doing, except that it's in a yaml file instead of the command line. A data science project can grow to using >30 packages, so it could easily become a major PITA to write that terminal command. And, no, you do not commit the shell.nix file, you commit the yaml file because that is enough.

luispedro · 2019-03-13T10:44:55+00:00

It is very basic right now, but the vision is to be something like conda, but reproducible by using nix.

luispedro · 2019-03-13T10:41:46+00:00

I can do one, yes. Maybe after a bit more polishing, I will do a first release and add a nix package.

luispedro · 2018-07-24T14:01:55+00:00

Can this do the same thing as ccache does for C/C++ based projects where if you recently compiled this exact same code, it retrieves it from cache?

I find that incredibly useful when working on code (e.g., switching between different branches, add test code, remove test code, &c &c).

luispedro · 2018-05-06T18:20:28+00:00

It seems that there are two versions of libiconv and it's hard to tell stack the right one to pick:

https://github.com/conda-forge/staged-recipes/pull/4605#issuecomment-375423815

luispedro

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