Parallel Squared Technology Institute

Scaling DNA sequencing is a notable success story.

Scaling protein analysis is harder since the proteome is a much taller mountain: www.nature.com/articles/s41...

@asimovpress.bsky.social writes about @parallelsq.bsky.social's approach to scale up proteomics.

Increasing throughput is particularly helpful when it also increases data quality. 🚀

YouTube video by Nikolai Slavov JMod: Joint modeling of mass spectra for enhanced multiplexing in the mass and time domains, SCP2025

The talk by Dr. Kevin McDonnell at #SCP2025 is on YouTube:

JMod: Joint modeling of mass spectra for enhanced multiplexing in the mass and time domains

youtu.be/qgqloCJJa1M?...

PTI will be represented at #ASMS2025 with with two posters (TP203 and ThP 533) and two talks (TOA 2:30 pm and WOA 8:30 am). Find us to hear about our PSMtag, and applications in Alzheimer's and aging biology!

🟦 Label-free single-cell proteomics (blue bars).

🟧 Multiplexed single-cell proteomics affords higher throughput (orange bars).

⬛️ Proteome depth & quantitative accuracy are comparable.

We aim to make the 🟧 bars taller.

www.parallelsq.org/psmtags

www.biorxiv.org/content/10.1...

We developed multiple interdependent technologies.

Together, they are opening up new opportunities:

www.parallelsq.org/blog/proteom...

#ASMS2025
Come here about the latest in real-time instrument control including applications to single cell proteomics (@parallelsq.bsky.social), #glycotime, and quantitative proteomics!

Find PTI's preprints at the PTI 𝑏𝑖𝑜𝑅𝑥𝑖𝑣 channel:

connect.biorxiv.org/relate/summa...

Furthermore, we identify sets of ubiquitin ligases whose levels robustly discriminate AD from non-AD samples. One subset exhibited consistent increases in AD, while another exhibited consistent decreases, revealing complex alterations to the ubiquitin system in AD.

www.biorxiv.org/content/10.1...

Alzheimer's disease (AD) is associated with numerous proteome changes.

We find large & consistent decrease in the abundance and stoichiometry of 20S proteasome subunits.
⬛️ It leads to abnormal accumulation of 20S substrate proteins.

🧵
biorxiv.org/content/10.1...

Leading these (and many ongoing) projects has been demanding, exhilarating & rewarding.

They required highly coordinated collaborations among diverse experts within PTI, MIT, MGH and beyond.

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These results required a highly coordinated development of synergistic technologies enabled by our FRO model and @convergentresearch.bsky.social.

Proteomics: Greater than the sum of its parts - PTI - Parallel Squared Technology Institute Over the past 2 years, PTI synergized advances in computational sciences, chemistry, biology and mass spectrometry to develop the next generation of applications and methods in single cell proteomics.

This week, we published 4 preprints reporting:

1️⃣ New new approaches for multiplexing & de-multiplexing proteomic data.
👉 Together, they scale throughput while preserving depth & accuracy.

2️⃣ Protein degradation dysregulation in Alzheimer's Disease

🧵
www.parallelsq.org/blog/proteom...

Ubiquitin-Proteasome System Dysregulation in Alzheimer's Disease Impacts Protein Abundance Alzheimer's disease (AD) is a relentlessly progressive, fatal neurodegenerative disorder associated with widespread aberrant proteomic changes. The full extent of protein dysfunctions in AD and their ...

We performed global and systematic proteome analysis of Alzheimer's disease (AD).

Our results suggest that decreased ubiquitin-proteasome system capacity and impaired clearance of proteins contribute substantially to proteopathic burden in AD.

www.biorxiv.org/content/10.1...

Increasing throughput in mass spec proteomics requires new ways to model the increased complexity of the spectra.
We are delighted to share JMod, our new open source software developed at @parallelsq.bsky.social , which enables new multiplexing approaches.

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www.biorxiv.org/content/10.1...

We just released JMod: an open source software supporting multiplexed DIA.

It supports parallelization in both the mass domain (plexDIA) using small mass offsets and in the time domain (timePlex).

It enabled 27-plex DIA & opens the door to further scaling 🚀

www.biorxiv.org/content/10.1...

Amazing amount of progress made advancing high throughput proteomics in such a short time from the team at @parallelsq.bsky.social 🚀

📊 Using stable isotopes of C/N/O, PSMtags increased protein datapoints from 4,340 (label-free) to 28,359 in the same time. We demonstrate 240 samples per day, but over 1,000 are possible with shorter runs.

That’s millions of protein data points per day.

🧪 Transforming biomedical discovery needs proteomics that is specific and accurate, but also faster and cheaper

@parallelsq.bsky.social is proud to introduce 9-plex PSMtags: a new mass tag that improves sequencing and increases throughput in sensitive proteomics 👇

www.biorxiv.org/content/10.1...

Multiplexed proteomics is getting a big boost 🚀

It's not just speed & scale ...
It's also data quality, depth, rich spectra improving de novo sequencing & accurate quantification.

biorxiv.org/content/10.1...

We paired 3-timePlex with @parallelsq.bsky.social's newly developed mass tag (PSMtag) used for 9-plexDIA.

This enables 27-plex, and we achieve >500 SPD with 25 minutes active chromatography per sample!

We are excited to introduce ‘time’ as a new domain for proteomics multiplexing!

It enables:
-Label-free multiplexing
-Combinatorial multiplexing with plexDIA

Using combined 9-plexDIA and 3-timePlex we demonstrate 27-plex DIA 🚀

A new dimension for multiplexing mass spec analysis -- time -- is enabling scaling up throughput at new levels.

We demonstrate 27-plex DIA enabling over 500 samples / day.

We project that timePlex will enable throughputs exceeding 1,000 samples / day.

www.biorxiv.org/content/10.1...

Unblock research bottlenecks with non-profit start-ups ‘Focused research organizations’ can take on mid-scale projects that don’t get tackled by academia, venture capitalists or government labs.

This past week I attended a meeting with the leadership of @convergentresearch.bsky.social FROs.

It was an uplifting and inspirational meeting !
A meeting centered on bold research motivated by compelling visions:

www.nature.com/articles/d41...

This week, PTI will be sharing 4 preprints, including:

⬛️ New tools & mass tags for plexDIA

⬛️ 27-plex DIA enabling 500 samples / day

⬛️ Improved de novo sequencing of peptides

⬛️ Protein degradation dysregulation in Alzheimer's

Check out @parallelsq.bsky.social for updates

🚀

Today is the day !

We are excited to share results and resources with the community !

We are looking forward to our symposium next Tuesday.

So excited to share the really cool work we're doing at PTI and celebrate our 2nd birthday at the same time! Come join us!!!

We are excited to share our technology & tools to empower research !

To learn more, join our Research Fest on April 22.

PTI is hosting Research Fest on April 22 and you are invited! PTI scientists will present on topics like improving sample throughput with tags for 9-plexDIA, increasing single-cell datasets to over 10,000 individual cells, and more.

RSVP today!
www.parallelsq.org/workshops-an...