Single-cell proteomics enables discoveries! It illuminates the frontiers of biomedical research.

Among all proteome changes in Alzheimer’s disease (AD), 20S proteasomes stand out. ⬛️ Their abundance strongly declines in AD patients. => This decline parallels a reduction in 20S substrate proteins and leads to abnormal protein accumulation in AD. biorxiv.org/content/10.1...

To facilitate technology dissemination, we will host a workshop in our laboratory. Register to secure a spot! Workshop participation is free with in-person conference registration but requires an advanced registration. To facilitate interactions and hands-on experience, participation is limited.

Research Fest highlighted PTI's scientific achievements to date as well as the team that made it all happen. We are thankful for the members on our team and the community who support our work, and wish everyone a Happy Thanksgiving. youtu.be/YFfeJqHC3tM

The multiplexing approaches that we are developing allow scaling up such rate measurements. timePlex, PSMtags, and JMod can all support increased throughput for 𝑖𝑛 𝑣𝑖𝑣𝑜 metabolic pulse experiments, and thus make dynamic protein analysis more scalable. Quote

More excellent work from @parallelsq.bsky.social ! So proud to be part of this team #TeamMassSpec #proteomics

No one is immune to aging but what exactly happens to our immune system as it ages? @thibaultcolombani.bsky.social takes a molecular dive into the immune system and talks about understanding age-induced immune altercations through single-cell proteomics. www.youtube.com/watch?v=WUU1...

Proteoforms matter: Protein functions change due to sequence variants and diverse modifications regulating their activities. 𝐓𝐨 𝐬𝐞𝐞 𝐛𝐢𝐨𝐥𝐨𝐠𝐲 (𝐚𝐧𝐝 𝐝𝐢𝐬𝐞𝐚𝐬𝐞) 𝐜𝐥𝐞𝐚𝐫𝐥𝐲, 𝐰𝐞 𝐧𝐞𝐞𝐝 𝐩𝐫𝐨𝐭𝐞𝐨𝐟𝐨𝐫𝐦-𝐥𝐞𝐯𝐞𝐥 𝐪𝐮𝐚𝐧𝐭𝐢𝐟𝐢𝐜𝐚𝐭𝐢𝐨𝐧 𝐚𝐭 𝐬𝐜𝐚𝐥𝐞. 1/2

𝐶𝑜𝑚𝑏𝑖𝑛𝑎𝑡𝑜𝑟𝑖𝑎𝑙 scaling may unlock a new level of throughput. This is enabling a long-awaited experiment ! Our team, led by Jason Derks, enabled combinatorial-scaling of mass spec proteomics throughput by developing multiplexing in the time domain, timePlex. 1/n

Combining this time domain multiplexing with mass domain multiplexing (plexDIA), we demonstrated combinatorial scaling of throughput. You can read about it www.biorxiv.org/content/10.1... and hear Jason describe it at the Parallel Squared Technology Institute Research Fest: youtu.be/2rLBk4IaZpk?...

Mahlon Collins is leading our discoveries in profiling the proteome of single neurons from Alzheimer's disease patients. He presents this research journey in a talk, "Discovering Alzheimer's disease protein dysfunctions with high throughput proteomics". youtu.be/UD8uSIfg7WY

@jasonderks.bsky.social presents "Increasing Mass spectrometry throughput using time encoded sample multiplexing" at Research Fest in Boston, MA on April 22, 2025. www.youtube.com/watch?v=2rLB...

And, we are back with another presentation from this year's Research Fest. PTI's Senior Computational Scientist, Kevin McDonnell, talks about developing joint modeling (aka JMod) of mass spectra for empowering multiplexed DIA proteomics. www.youtube.com/watch?v=plK4...

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...

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.

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

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. 🚀

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. 1/2

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...

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. 1/7 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...

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...