Parallel Squared Technology Institute

YouTube video by Parallel Squared Technology Institute Tags for improving peptide sequencing and throughput in sensitive proteomics | Maddy Yeh, Mark Adamo

Throwback Thursday continues with a presentation by Maddy Yeh and Mark Adamo from Research Fest: "Tags for improving peptide sequencing and throughput in sensitive proteomics".

Watch on YouTube: www.youtube.com/watch?v=jA2I...

Transformative Opportunities for Single-Cell Proteomics Many pressing medical challenges, such as diagnosing disease, enhancing directed stem-cell differentiation, and classifying cancers, have long been hindered by limitations in our ability to quantify p...

The counting statistics for single-cell MS support accurate estimates of protein abundance in single cells, which is essential for quantitative analysis.

Further, measuring and modeling protein degradation is key to biological interpretations.

pubs.acs.org/doi/10.1021/...

Earlier this year, @parallelsq.bsky.social hosted a research fest.

We began with a broad perspective:
◾️ A century of remarkable progress! Proteomics drove conceptual discoveries and medical treatments.

Listen to what's next!

Proteomics: The arc of progress
youtu.be/Sc2QLXb84XI?...

Congrats to @e11bio.bsky.social on developing and showcasing PRISM for mapping brain wiring.

YouTube video by Parallel Squared Technology Institute Proteomics: The arc of progress | Nikolai Slavov

It's good to look back and see how far we have come since Research Fest took place almost six months ago.

Over the next few weeks, we will post some throwback videos from the presentations. Let's start with opening remarks by PTI's Director, @slavov-n.bsky.social:

youtu.be/Sc2QLXb84XI

Our large scale measurements of protein functions and conformations can help realize the potential of AI.

When developing AI models, we emphasize careful validation & rigorous benchmarking.

I am looking forward to ICSB next week.

I will present:
1⃣ New technology from @parallelsq.bsky.social:
parallelsq.org/blog/proteom...

2⃣ New biology from @slavovlab.bsky.social
biorxiv.org/content/10.1...

@jasonderks.bsky.social is presenting at iSCMS! Come by this Saturday afternoon around 2pm to hear his talk: "Increasing proteomics throughput by multiplexing in the mass and time domains".

singlecellms.org?page_id=442

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.

We developed approaches to increase the parallelization of proteomics in the mass and time domains and demonstrated 27x increased throughput.

They can scale further the throughput of the metabolic pulse proteomics demonstrated by @andrewleduc.bsky.social et al.

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

Multiplexed DIA enabled multimodal proteomics of ~ 10³ single cells, including quant of protein synthesis & degradation rates.

Our technologies can increase the multiplexing along different dimensions (mass, time) and thus scale up throughput further to ~ 10⁴ - 10⁵ single cells.

🔽

We quantified mRNA abundance, translation, protein abundance, protein degradation and cell growth across thousands of single cells from a mammalian tissue.

The results revealed 𝐜𝐨𝐦𝐩𝐥𝐞𝐱 regulation & 𝐬𝐢𝐦𝐩𝐥𝐞 organizing principles:

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

🧵

Science communication is a key part of our mission, so thank you @juliabauman.bsky.social for this video about PTI's single cell proteomics research!

PTI is growing and we are looking for more scientists to join our team!

Neurodegenerative Disease Senior Scientist: jobs.lever.co/convergentre...

Computational Biologist: jobs.lever.co/convergentre...

Research Chemist: jobs.lever.co/convergentre...

We share our technologies to maximize the benefit for the community.

PSMtags enable 9-plexDIA with better sequencing and multiplexing.

PSMtags support sensitive proteomic analysis of over 1,000 samples / day.

parallelsq.org/psmtags

The registration for SCP2026 is open !

Join us next July for the the 9th Single Cell Proteomics Conference.

single-cell.net/proteomics/s...

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...