Insights into proteomics in 2024 from blog traffic numbers!

The dashboard of this blog gives me interesting insights at times. I get easy metrics for what posts people (completely anonymous) engage with. And where (geographically) traffic is coming from as well as some insights into what links people are coming from, to some degree. Like when Twitter had a lot of functional features I could tell that people were coming from Twitter links that were posted. None of that works since...well....you know....

While I've got 2 hours of sleep because one of those adorable little germ factories gave my adorable little germ factory the worst virus of his entire life, I thought I'd summarize some of what I see when I log in because I don't have enough sleep to remember what I was actually planning to do. 

Insight #1: If I want to decrease traffic, write about single cell proteomics (SCP)

While the outside world really seems to care about SCP, while still being largely confused about what it is, who is doing it, and why the scSeq core can't help them with it, my small reader base is not interested in today's newest advance. Since I have been personally interested, this has directly hurt blog viewership numbers. For real, we're talking crushing readership numbers. The only thing worse is to write about Metabolomics. 

Insight #2: If I want to attention post a tutorial or talk about a "next gen" proteomics technology

Here are a couple examples of posts with recent traffic metrics. These are between 4 and 10x more traffic than any recent SCP post. Highlighting SomaScan's ....trepidation....for actual quantitative comparisons and how MS1 libraries work. 

Same here, recent post where that group forced one protein through a NanoPore and just a simple tutorial (thanks to Ed Emmott's lab making an XML) for how to process data that was not -at the time -natively compatible with MaxQuant (I'm sure it is now). Big engagement numbers relative to other posts.

Insight #3: - The big one - People really need very basic help with proteomics. Check out the recent traffic to some of these permanent pages!

The "terminology translator" has always been a major draw to the blog. "What is this weird acronym the guy in the basement used that I don't know?" But "what is proteomics" still gets a lot of hits even though I made a long drawn out analogy about a car I was obsessed with when I was a kid. And both "resources for newbies" and "now I have a protein list" get slammed with new traffic, which makes me realize how important it is that I update these once in a while. I'm sure I'll physically cringe when I see how old some of the links in those posts/pages are. 

We see this exact same thing with r/proteomics, though most of the stuff appears to go to r/massspectrometry or r/bioinformatics first. A lot of the traffic is "how do I process these data in DIA-NN". "What does this q-value thing mean?" 

This is all good stuff, I think. It means that new people are engaging with proteomics technology. And -- since you still can't get a degree (though many European schools have formal coursework in mass spectrometry and proteomics) people need help with these things. The bad news is that they might just be Googling it and ending up at a site maintained by someone who has less time to put into it every year. 

If you are generating high quality freely/openly available content to help people new to proteomics please reach out so I can direct people your way! 

More amazing archaeology proteomics - sex determination from teeth?!?!

 

Rapidly climbing the list of "who I want to be when I grow up" thanks to a diffuse and seemingly unfocused series of paradigm shifting studies is one Jesper V. Olsen. (Words in italics are from one of my favorite recent podcasts we recorded) 

It isn't that diffuse because Olsen lab has been doing some amazing stuff pushing the boundaries of what we thought we could do with archaeological samples - with proteomics. But when you look at the amazing disease work on top it's easy to think they're all over the place. As a whole it's just amazing lines of productivity in multiple directions. Does that justify the 2 invertebrate studies we've written and haven't submitted yet because I'm trying to build a coherent theme to my CV? Meh. I guess we'll see.  

When you find human archaeological samples you can tell sex if they are very very well preserved. Which is also very very rare. Teeth, however, are really tough. So....if you want sex information from these materials you can guess... or you can use laser etching to get down to proteins in teeth and do PRMs and then load your data into this Shiny interface and....now you know for sure....

RIGHT?!?!?! 

We're out of the backwater!

I'll probably be backdating some posts. I've been busy busy busy, but I haven't slipped far from my reading a paper every day rule, its just finding time to summarize and post them here. 

Need some motivation to get back at it? How 'bout us cracking another big industry magazine?

You can check it out here.  (Shoutout to Dr. Luke Gamon for the heads up on this!) 

Okay...so I was thinking about what backwater was and it reminded me of an old Saturday morning cartoon show. Surprisingly, Google could figure out what I was thinking about.....

FeMS - Navigate those career transitions!

 

The great Females in Mass Spectrometry organization is holding an awesome panel discussion at US HUPO on 3/10! Look at that lineup and career stage pacing. 

Can't make it? FeMS has tons of great content all the time! You can find out what they're up to here.

Phosphopeptide retention time prediction numbers!

 

We all know phosphorylated a peptide changes the retention time. How much, though? And how much does changing the brand/type of C-18 resin change that shift? (Where this study really shines!). 

BOOOM! 

Ion mobility at 1,100 resolution with escalator ramping!

 

Ion mobility is finally showing results to back up the promise we've been told it had for decades. People are doing amazing things with the aid of FAIMS. Most commercial units of that have resolutions around 10. 

The TIMS thing that took Bruker selling 1 mass spectrometer every 3 years to someone who was either gullible or really needed an FTICR to ALMOST $1 BILLION IN REVENUE IN 2023 has a resolution around 100-200 depending on how you measure it.

You can get "gas phase NMR" for your Thermo instruments, which is a high resolution FAIMS from HeartStone that is in excess of 200 resolution.

But 1,000 resolution????  "Lossless"? If IMS is your thing, this is your paper! 

Reflections on the EuBiC Winter School (Guest blogger post!)

As the snow was not so gently falling on the charming town of Winterberg, Germany, the stage was set for the EuBIC-MS (https://eubic-ms.org/) Winter School 2024 - an engaging five-day conference dedicated to (computational) proteomics, mass spectrometry, and bioinformatics. The days were filled with keynote talks, workshops, and great scientific and non-scientific discussions!  Since the first edition in 2017, this biennial event has brought together early-stage PhD students eager to step into computational proteomics and experts from the field.

The conference set off with educational workshops arranged by us PhD students in the PROTrEIN (https://protrein.eu/) training network. We held several parallel workshops on mass spectrometry-based proteomics workflows, PTM identification, and prediction models. For us in PROTrEIN it was a great opportunity to arrange these workshops to really see how far we have come since the project started! In our kick-off back in September 2021 we were the ones attending similar workshops, and now, 2.5 years later we are grateful to have the opportunity to host such workshops. In parallel with our workshops, there were also workshops about demystifying GitHub actions and a workshop held by MSAID about analysis using their tool CHIMERYS. 

Attendees would certainly agree that the poster session on Tuesday evening was particularly engaging. Young researchers from diverse backgrounds had the opportunity to showcase their latest work which led to many innovative and stimulating discussions. 

Despite the flurry of academic sharing and learning, we did not lose sight of the fun. Ben & Ben (Orsburn & Neely) did a live recording of their podcast “The Proteomics Show” with a special guest from the audience! It was really interesting to see Ben & Ben in action and get behind the scenes a bit. Ben (Orsburn) also talked about his journey writing this blog - which gave us some insight into what it really entails. Wednesday concluded with a social event that saw us sledding down the snowy slopes of Winterberg, a fun and memorable experience that brought us all closer together. 

We must not forget to mention the 10 great keynote talks that covered diverse topics in the field. From isotopes to good practice of data sharing to single-cell proteomics and FASTA files of sealion proteomes. Many of the keynote speakers had also prepared workshops where the participants could dive deeper into the topics. 

Looking back, the EuBIC-MS Winter School 2024 was more than just a conference. It was a gathering of a great community of people, a platform for learning and sharing, and a testament to the exciting developments in the field of proteomics, mass spectrometry and bioinformatics. Thanks to everyone who was part of the organizational team, all the keynote speakers, all the participants and to Ben for letting us use his platform to share about our experience at this event! 

Back to Ben: 

This blog post was written as part of the EuBIC Scientific Communications workshop by 2 great up and coming scientists!

Louise Marie Buur who is a PhD student in the Bioinformatics Research Group at University of Applied Sciences Upper Austria in Hagenberg and PROTrEIN early stage researcher. (LinkedIn here) 

and 

Arthur Grimaud who is a also a PROTrEIN early stage research and PhD Student in Computational Proteomics at Syddansk Universitet - University of Southern Denmark. (LinkedIn here)

In addition to getting their PhDs in things that would make them enormously employable whenever they're done (just pop in on the Old Time Proteomics Radio Hour to hear PIs trying to steal each other's bioinformaticians) they also run a blog for PROTrEIN (check it out here)! I'm working on putting up a permanent page over there ----> somewhere that is title something like "real proteomics blogs" or "...blogs I read..." or something. 

Automatable cell surface proteomics (surface-omics) with magnetic beads!

 

70% of our drugs target proteins at the cell surface! Real number.

And mass spectrometry based proteomics is....sort of lousy at identifying them! There are bunches of methods out there, but what would you do if you needed to look at a lot of samples in a semi- or fully automated way? 

Okay...when you put the entire schematic together at the top it does look like a..lot...but when you really break it down into constituents it probably is the easiest method for Cell Surface Proteomics (cell surfaceomics?) that I've seen. PLUS all these things are amenable to automation! 

Now, there are a lot of methods out there, with my go to being Josip Blonder's classic work on the topic but the weakness of this method and several of the others is that it enriches membranes indiscriminately (which probably still helps) but newer methods like the topic story of this post do alter the actual proteins on the outside of the cell so you are selectively enriching for those. Looking for the next drug target en masse? This method might be a great place to start!  

Next question, of course, is "can I load these data into SurfaceGenie?" I bet you can! 

So....how about 1.4min plasma proteomics?

 

LCMS based proteomics isn't a "high throughput" technology, right? I mean, you hear it all the time. I sure as hell hear it ALLLLLLLLLLLLL the time here in Genome Alley. "If you get the $20M transcriptomics platform and you load 1,000 library preps on it, it'll knock it out IN A DAY."

In that same amount of time....you could also knock out a pretty impressive depth of 1,000 human plasma samples...

I think this guy from Annapolis is over-reacting. This isn't the first time we've seen some crazy numbers out of flow injection proteomics from this PI. He's been messing around with this stuff since he was in Wisconsin, but with ever increasing numbers.

But on plasma? With the 10-order of magnitude concentration range? This is big time. FAIMS was used here, but - FAIMS is great, but it's got a resolution of approximately 10. For that reason...use FAIMS, don't use FAIMS, it's not that big of a difference for most things, right? Running a 2.8 minute injection on this setup would give you about a resolution of 2, right? 

These nanoparticles might need a serious investigation. Super cool study all around! 

ProteoBench is coming! Register to see what the fuss is all about 2/27!

 

Regardless of what the outside world might think we have, the proteomics community (and - to be fair -genomics isn't all there yet, either) fully complete, FAIR (which is also a thing), trackable and reproducible workflows. 

It's actually a big deal to a lot of people out there.

You might have heard the word "ProteoBench" come up on THE Proteomics Show (is that still going on?) on a couple of recent episodes.

Find out WTF it is on 2/27! It's a seriously big deal. 

Proteomic Testing Act Passed! What it means!

 

The biggest news for proteomics for 2024 isn't some silly expensive new instrument. It isn't dueling labs trying to see who can throw the most money at a single cell. It is absolutely, without a doubt, this little tiny bit of legislation last week. More details here! 

For a decent analysis of what this could mean you can check out this paper from last year.  (It should be open access). 

The short story is that one of the biggest hurdles in getting proteomic diagnostics out there in the world helping people has been kicked right over. There is a billing mechanism so that labs performing these tests can get paid for said tests. 

If you're someone who filled out the recent Twitter survey on what "clinical proteomics" means last year and you selected "analyzed the proteomes of human samples" stop reading right here and go back to what you're doing. This news is not for you. This news is for the minority of people who got the answer correct. Despite the.....things.....that often manage to get published in the "journal" called "Clinical Proteomics", running HeLa dilutions is not what this is about.  

Clinical proteomics is the application of protein measurement technologies to inform a clinician of information to aid in patient diagnosis. Any sort of clinical assay needs to be rock solid. From a thorough (and special) validation of the instrument that you've purchased (if not a special approval from the design of the device to qualify it for medical testing) through the strict monitoring of where that sample is in your lab - at all times - and what has been done to it, it's serious stuff. Even your scales and pipettors have to be manufactured in a compliant environment with calibrations checked and monitored routinely. Randomly people will show up by surprise and try to find you slouching. Failed that 4pm QC? Cancel plans. You're recalibrating and then you are randomly pulling samples you ran between the last QC that passed. You slipped 2 standard deviations in more than 10% of the random samples? You're re-running every. single. one.  of them. That's what it's like in clinical chemistry. For real.

Whew. With that out of the way....

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAHHHHHHHHHHHH!!!!!!!!!!!!!!

This is so huge for anyone with aspirations of really really doing clinical proteomics. This is the gateway to getting the attention of company's to take those biomarkers you found for early detection of disease A and condition B actually out there in the wild where they will really and truly do things. 

Self-serving entry time ---> if you've got biomarkers and you need help getting that panel out there in the world, I'm willing to talk. If you're an investor hoping to capitalize on this new market, I just got my DUNS. Clearly this blog is what everyone here knows me for, but I started doing clinical chemisty 21 years ago. What a lot of business people know me for is as the sole inventor of the very first (and still possibly only) high resolution LCMS assay to operate under ISO and US DOH regulatory compliance guidelines. No joke, I took a brand new quadrupole Orbitrap and made it a fully compliant testing device. Pain. In. The. Butt. But it would be easier to do it a second, third, or twelfth time. 

Either way, it's time to stop screwing around and help people! 

Genes are not the blueprint for life. Duh.

 

While it would be fun to put in a lot of gifs here, I'm going to do just one. And it was tough to not drop 4 SpongeBobs somewhere here.

This is a review of a book and both the book and the reviewer seem to have gotten past what 99.99% of Genome Alley has not, and started to think that maybe -just maybe - Petabytes of genomic data aren't going to fix all of medicine. 

No joke, though, this book is next up on my list. I finally started Ian Christie's magnum opus - and, yes, it is probably going to be worth it, but that dude can expound....so it might be a while....

Pulled Tip Columns are back! ESI Source Solutions!

If you're still trying to find a vendor for pulled tip custom columns, there is finally one in the US again!

What are those holes in the US HUPO agenda each evening? They're fun VMO functions!

 

The US Human Proteomics Organization's 20th anniversary is coming up so fast that the Agenda is now up! 

Dr. Neely said this better...so...

...we did a play by play of this year's agenda! 

What we didn't cover were the 2 evening holes in the Agenda that didn't say anything. As the chair of the VMO I felt like I should know which night was what, as they are our activities. HOWEVER.

Monday night is going through the winning entries of the VMO Proteomics Video Competition! We extended the deadline until 2/15 for late breaking entries. Come on, you clever young tik tokers, and short YouTubers we know you've got something up your sleeves. Reminder, there is prize money.

Tuesday night's unlisted slot is the (requested by the leadership, for the record, I think it's a poor idea) live recording of THE Proteomics Show. It worked in Germany. I'm skeptical about reproducing it as well somewhere that I don't know the language, but US HUPO funds the program, so we're gonna do it anyway! 

Single Cell Proteomics made Gen News!

I know proteomics people are probably tired of hearing about single cell proteomics from every angle, but the rest of the world can't seem to get enough of it! 

More proof? Check out this brand new article in Genetic Engineering News! 

It's a surprisingly well-balanced analysis of where we are from a technology stand point. Of course, the absurd numbers Karl's group has been showing off makes the article, and you can't write an article on SCP without Slavov lab. Our field's favorite picoliter robotics systems are highlighted as well as my group's early results on the ZenoTOF and TIMSTOF Flex! Perhaps the 7am seminar isn't the best place to get a sound bite from me about the difficulties in making nanoflow chromatography accessible to non-mass spec nerds, but sometimes you need some emotion in your words? 

The final US HUPO 2024 Guest Speaker podcast is live Dr. Mark Flory!

 

The US HUPO VMO group votes (every?) year on the invited speakers for US HUPO that they'd most like to have us interview on THE Proteomics Show podcast.

These are the podcasts where there is sortofa set structure. If you listen to podcasts and are going to Portland - this is our Portland expert! Dr. Flory also has an amazing career journey from academia, to industry, to academia, to industry and to his current home. There are some great insights for people starting out on their careers like - how 4 years in one spot in the Bay Area is almost an unusual amount of time. Super cool stuff. 

And you might notice this one is a lot longer than the other ones. I won't tell you why, you'll just have to find out. 

Get it wherever you get those podcast things.