Nikolai Slavov
@slavov-n.bsky.social
Mentor, scientist & engineer. Having fun in @slavovlab.bsky.social and Parallel Squared Technology Institute @parallelsq.bsky.social with biology & single-cell proteomics.
https://nikolai.slavovlab.net
https://nikolai.slavovlab.net
Where is the dislike button ?
November 19, 2025 at 2:00 PM
Where is the dislike button ?
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.
www.biorxiv.org/content/10.1...
⬛️ Their abundance strongly declines in AD patients.
=> This decline parallels a reduction in 20S substrate proteins and leads to abnormal protein accumulation in AD.
www.biorxiv.org/content/10.1...
November 19, 2025 at 1:38 PM
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.
www.biorxiv.org/content/10.1...
⬛️ Their abundance strongly declines in AD patients.
=> This decline parallels a reduction in 20S substrate proteins and leads to abnormal protein accumulation in AD.
www.biorxiv.org/content/10.1...
Protein regulation varies across single cells, cell types, tissues, and organs.
The brain proteome is highly sculpted by protein degradation.
Why ?
This is our model: biorxiv.org/content/10.1...
The brain proteome is highly sculpted by protein degradation.
Why ?
This is our model: biorxiv.org/content/10.1...
November 17, 2025 at 1:14 PM
Protein regulation varies across single cells, cell types, tissues, and organs.
The brain proteome is highly sculpted by protein degradation.
Why ?
This is our model: biorxiv.org/content/10.1...
The brain proteome is highly sculpted by protein degradation.
Why ?
This is our model: biorxiv.org/content/10.1...
How do plants orient towards light ?
In the absence of obvious physical sensing organs like lenses, how do plants work out the precise direction from which light is coming ?
In the absence of obvious physical sensing organs like lenses, how do plants work out the precise direction from which light is coming ?
November 16, 2025 at 12:34 PM
How do plants orient towards light ?
In the absence of obvious physical sensing organs like lenses, how do plants work out the precise direction from which light is coming ?
In the absence of obvious physical sensing organs like lenses, how do plants work out the precise direction from which light is coming ?
Fitness influencers promote super-high-protein diets, and protein-fortified foods and protein supplements form a market worth tens of billions of USD.
Yet, studies show there’s only so much protein the body can use.
Yet, studies show there’s only so much protein the body can use.
November 15, 2025 at 4:17 PM
Fitness influencers promote super-high-protein diets, and protein-fortified foods and protein supplements form a market worth tens of billions of USD.
Yet, studies show there’s only so much protein the body can use.
Yet, studies show there’s only so much protein the body can use.
Dimensionality reduction can see structures that do not exist and miss structures that exist.
𝐓𝐡𝐞 𝐬𝐢𝐦𝐩𝐥𝐞𝐬𝐭 𝐞𝐱𝐩𝐥𝐚𝐧𝐚𝐭𝐢𝐨𝐧 𝐢𝐬𝐧’𝐭 𝐚𝐥𝐰𝐚𝐲𝐬 𝐭𝐡𝐞 𝐛𝐞𝐬𝐭 𝐨𝐧𝐞.
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𝐓𝐡𝐞 𝐬𝐢𝐦𝐩𝐥𝐞𝐬𝐭 𝐞𝐱𝐩𝐥𝐚𝐧𝐚𝐭𝐢𝐨𝐧 𝐢𝐬𝐧’𝐭 𝐚𝐥𝐰𝐚𝐲𝐬 𝐭𝐡𝐞 𝐛𝐞𝐬𝐭 𝐨𝐧𝐞.
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November 14, 2025 at 12:45 PM
Dimensionality reduction can see structures that do not exist and miss structures that exist.
𝐓𝐡𝐞 𝐬𝐢𝐦𝐩𝐥𝐞𝐬𝐭 𝐞𝐱𝐩𝐥𝐚𝐧𝐚𝐭𝐢𝐨𝐧 𝐢𝐬𝐧’𝐭 𝐚𝐥𝐰𝐚𝐲𝐬 𝐭𝐡𝐞 𝐛𝐞𝐬𝐭 𝐨𝐧𝐞.
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𝐓𝐡𝐞 𝐬𝐢𝐦𝐩𝐥𝐞𝐬𝐭 𝐞𝐱𝐩𝐥𝐚𝐧𝐚𝐭𝐢𝐨𝐧 𝐢𝐬𝐧’𝐭 𝐚𝐥𝐰𝐚𝐲𝐬 𝐭𝐡𝐞 𝐛𝐞𝐬𝐭 𝐨𝐧𝐞.
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Current efforts focus on predicting transcriptional responses to gene silencing.
Even if spectacularly successful, they leave open key questions:
◾️Functions of genetic mutations & polymorphisms
◾️Proteoform functions
◾️Protein abundance regulation
Biology is complex.
Even if spectacularly successful, they leave open key questions:
◾️Functions of genetic mutations & polymorphisms
◾️Proteoform functions
◾️Protein abundance regulation
Biology is complex.
November 13, 2025 at 3:39 PM
Current efforts focus on predicting transcriptional responses to gene silencing.
Even if spectacularly successful, they leave open key questions:
◾️Functions of genetic mutations & polymorphisms
◾️Proteoform functions
◾️Protein abundance regulation
Biology is complex.
Even if spectacularly successful, they leave open key questions:
◾️Functions of genetic mutations & polymorphisms
◾️Proteoform functions
◾️Protein abundance regulation
Biology is complex.
Even when the overall correlation is positive, many functional sets of proteins exhibit distinct regulation.
November 12, 2025 at 12:53 PM
Even when the overall correlation is positive, many functional sets of proteins exhibit distinct regulation.
The protein and mRNA abundance voronoi diagrams offer remarkably different perspectives.
Each tile in the maps represents a gene product; its size is proportional to the fraction of the gene product in hepatocytes.
Each tile in the maps represents a gene product; its size is proportional to the fraction of the gene product in hepatocytes.
November 12, 2025 at 12:53 PM
The protein and mRNA abundance voronoi diagrams offer remarkably different perspectives.
Each tile in the maps represents a gene product; its size is proportional to the fraction of the gene product in hepatocytes.
Each tile in the maps represents a gene product; its size is proportional to the fraction of the gene product in hepatocytes.
A reminder that the abundance of 'housekeeping' proteins varies significantly across cells and tissues.
GAPDH is often slandered as a 'housekeeping' protein, and its abundance varies significantly across human tissues.
How do you define a 'housekeeping' protein ?
GAPDH is often slandered as a 'housekeeping' protein, and its abundance varies significantly across human tissues.
How do you define a 'housekeeping' protein ?
November 11, 2025 at 11:56 AM
A reminder that the abundance of 'housekeeping' proteins varies significantly across cells and tissues.
GAPDH is often slandered as a 'housekeeping' protein, and its abundance varies significantly across human tissues.
How do you define a 'housekeeping' protein ?
GAPDH is often slandered as a 'housekeeping' protein, and its abundance varies significantly across human tissues.
How do you define a 'housekeeping' protein ?
The protein concentration in the cytoplasm is so high that the average protein has a water hydration shell with a thickness of only ≈ 10 water molecules separating it from the adjacent protein hydration shell.
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November 10, 2025 at 12:57 PM
The protein concentration in the cytoplasm is so high that the average protein has a water hydration shell with a thickness of only ≈ 10 water molecules separating it from the adjacent protein hydration shell.
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Large models are difficult to evaluate.
Fundamentally difficult.
This difficulty is not well communicated in enthusiastic social media posts advertising predictive performance.
2/2
open.substack.com/pub/gmdbioin...
Fundamentally difficult.
This difficulty is not well communicated in enthusiastic social media posts advertising predictive performance.
2/2
open.substack.com/pub/gmdbioin...
November 9, 2025 at 4:11 PM
Large models are difficult to evaluate.
Fundamentally difficult.
This difficulty is not well communicated in enthusiastic social media posts advertising predictive performance.
2/2
open.substack.com/pub/gmdbioin...
Fundamentally difficult.
This difficulty is not well communicated in enthusiastic social media posts advertising predictive performance.
2/2
open.substack.com/pub/gmdbioin...
"Some participants have already found a way to hack the score, exposing fundamental flaws in how bio-foundation models are evaluated."
𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐧𝐠 𝐦𝐨𝐝𝐞𝐥𝐬 𝐢𝐬 𝐡𝐚𝐫𝐝. 𝐈𝐭 𝐧𝐞𝐞𝐝𝐬 𝐦𝐨𝐫𝐞 𝐚𝐭𝐭𝐞𝐧𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐫𝐞𝐬𝐨𝐮𝐫𝐜𝐞𝐬.
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𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐧𝐠 𝐦𝐨𝐝𝐞𝐥𝐬 𝐢𝐬 𝐡𝐚𝐫𝐝. 𝐈𝐭 𝐧𝐞𝐞𝐝𝐬 𝐦𝐨𝐫𝐞 𝐚𝐭𝐭𝐞𝐧𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐫𝐞𝐬𝐨𝐮𝐫𝐜𝐞𝐬.
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November 9, 2025 at 4:08 PM
"Some participants have already found a way to hack the score, exposing fundamental flaws in how bio-foundation models are evaluated."
𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐧𝐠 𝐦𝐨𝐝𝐞𝐥𝐬 𝐢𝐬 𝐡𝐚𝐫𝐝. 𝐈𝐭 𝐧𝐞𝐞𝐝𝐬 𝐦𝐨𝐫𝐞 𝐚𝐭𝐭𝐞𝐧𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐫𝐞𝐬𝐨𝐮𝐫𝐜𝐞𝐬.
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𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐧𝐠 𝐦𝐨𝐝𝐞𝐥𝐬 𝐢𝐬 𝐡𝐚𝐫𝐝. 𝐈𝐭 𝐧𝐞𝐞𝐝𝐬 𝐦𝐨𝐫𝐞 𝐚𝐭𝐭𝐞𝐧𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐫𝐞𝐬𝐨𝐮𝐫𝐜𝐞𝐬.
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A beautiful example illustrating a difference between plasma protein analysis by different technologies.
Peptides from some proteoforms correlate better to epitope-based measurements (Olink) than others.
The measurements differ because they reflect different proteoforms !
Peptides from some proteoforms correlate better to epitope-based measurements (Olink) than others.
The measurements differ because they reflect different proteoforms !
November 8, 2025 at 2:03 PM
A beautiful example illustrating a difference between plasma protein analysis by different technologies.
Peptides from some proteoforms correlate better to epitope-based measurements (Olink) than others.
The measurements differ because they reflect different proteoforms !
Peptides from some proteoforms correlate better to epitope-based measurements (Olink) than others.
The measurements differ because they reflect different proteoforms !
Proteoforms encoded by the same gene have different interactomes.
This challenges:
1⃣ The interpretation of data from affinity reagents directed towards shared epitopes.
2⃣ The assignment of functions to genes.
When will biological research focus on such functional differences?
This challenges:
1⃣ The interpretation of data from affinity reagents directed towards shared epitopes.
2⃣ The assignment of functions to genes.
When will biological research focus on such functional differences?
November 6, 2025 at 12:52 PM
Proteoforms encoded by the same gene have different interactomes.
This challenges:
1⃣ The interpretation of data from affinity reagents directed towards shared epitopes.
2⃣ The assignment of functions to genes.
When will biological research focus on such functional differences?
This challenges:
1⃣ The interpretation of data from affinity reagents directed towards shared epitopes.
2⃣ The assignment of functions to genes.
When will biological research focus on such functional differences?
My commute to PTI.
November 3, 2025 at 2:36 PM
My commute to PTI.
Discuss.
What are the implications for student learning and evaluation.
What are the implications for student learning and evaluation.
November 2, 2025 at 6:19 PM
Discuss.
What are the implications for student learning and evaluation.
What are the implications for student learning and evaluation.
George Boole was born exactly 210 years ago today. He was largely self‑taught, the son of a shoemaker, yet founded what we now call Boolean algebra.
November 2, 2025 at 6:04 PM
George Boole was born exactly 210 years ago today. He was largely self‑taught, the son of a shoemaker, yet founded what we now call Boolean algebra.
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.
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Our team, led by Jason Derks, enabled combinatorial-scaling of mass spec proteomics throughput by developing multiplexing in the time domain, timePlex.
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November 1, 2025 at 4:59 PM
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
Our team, led by Jason Derks, enabled combinatorial-scaling of mass spec proteomics throughput by developing multiplexing in the time domain, timePlex.
1/n
One gene can code for proteoforms with:
◼️ different functions
◼️ different sequences
◼️ different regulation
◼️ different cell type expression
Such examples should inform the interpretation of gene deletion experiments seeking to infer "gene functions".
◼️ different functions
◼️ different sequences
◼️ different regulation
◼️ different cell type expression
Such examples should inform the interpretation of gene deletion experiments seeking to infer "gene functions".
November 1, 2025 at 1:51 PM
One gene can code for proteoforms with:
◼️ different functions
◼️ different sequences
◼️ different regulation
◼️ different cell type expression
Such examples should inform the interpretation of gene deletion experiments seeking to infer "gene functions".
◼️ different functions
◼️ different sequences
◼️ different regulation
◼️ different cell type expression
Such examples should inform the interpretation of gene deletion experiments seeking to infer "gene functions".
Nascent proteins may be phosphorylated during translation & the phosphosite buried in the protein’s inner core
Such buried phosphosite are found in ~ 1/3 of the phosphorylated human proteins.
They can influence protein abundance (👇), providing another example for proteoform specific regulation.
Such buried phosphosite are found in ~ 1/3 of the phosphorylated human proteins.
They can influence protein abundance (👇), providing another example for proteoform specific regulation.
October 31, 2025 at 10:31 AM
Nascent proteins may be phosphorylated during translation & the phosphosite buried in the protein’s inner core
Such buried phosphosite are found in ~ 1/3 of the phosphorylated human proteins.
They can influence protein abundance (👇), providing another example for proteoform specific regulation.
Such buried phosphosite are found in ~ 1/3 of the phosphorylated human proteins.
They can influence protein abundance (👇), providing another example for proteoform specific regulation.
... the changes in protein abundance.
These changes in protein abundance and clearance are functionally coordinated and affect multiple pathways, including proteasomes, spliceosomes, and chromatin regulators.
These changes in protein abundance and clearance are functionally coordinated and affect multiple pathways, including proteasomes, spliceosomes, and chromatin regulators.
October 30, 2025 at 11:28 AM
... the changes in protein abundance.
These changes in protein abundance and clearance are functionally coordinated and affect multiple pathways, including proteasomes, spliceosomes, and chromatin regulators.
These changes in protein abundance and clearance are functionally coordinated and affect multiple pathways, including proteasomes, spliceosomes, and chromatin regulators.
Aging is associated with changes in protein abundance in many organs and tissues.
We find that the protein changes are cell-type specific, and thus muted in previous bulk analysis.
Protein clearance rates change with age and drive the ...
www.biorxiv.org/content/10.1...
We find that the protein changes are cell-type specific, and thus muted in previous bulk analysis.
Protein clearance rates change with age and drive the ...
www.biorxiv.org/content/10.1...
October 30, 2025 at 11:28 AM
Aging is associated with changes in protein abundance in many organs and tissues.
We find that the protein changes are cell-type specific, and thus muted in previous bulk analysis.
Protein clearance rates change with age and drive the ...
www.biorxiv.org/content/10.1...
We find that the protein changes are cell-type specific, and thus muted in previous bulk analysis.
Protein clearance rates change with age and drive the ...
www.biorxiv.org/content/10.1...
Quantitative assessment of Xi contributions to X chromosome gene expression.
October 27, 2025 at 11:40 AM
Quantitative assessment of Xi contributions to X chromosome gene expression.
The ‘‘inactive’’ X chromosome (Xi) is active.
Xi regulates gene expression from the active X.
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Xi regulates gene expression from the active X.
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October 27, 2025 at 11:40 AM
The ‘‘inactive’’ X chromosome (Xi) is active.
Xi regulates gene expression from the active X.
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Xi regulates gene expression from the active X.
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