The majority of isoform pairs (of alternatively spliced transcripts) share less than 50% of their interactions.
In the context of interactome networks, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other.
In the context of interactome networks, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other.
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 1:41 PM
The majority of isoform pairs (of alternatively spliced transcripts) share less than 50% of their interactions.
In the context of interactome networks, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other.
In the context of interactome networks, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other.
New preprint alert from my lab: Using long-read RNA sequencing, we developed an updated PSI metric, PSI-LR, which quantifies the expression of the multiple TTN transcript isoforms and predicts advanced heart failure risk in patients with cardiomyopathy due to TTN-TV.
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
November 4, 2025 at 9:54 PM
New preprint alert from my lab: Using long-read RNA sequencing, we developed an updated PSI metric, PSI-LR, which quantifies the expression of the multiple TTN transcript isoforms and predicts advanced heart failure risk in patients with cardiomyopathy due to TTN-TV.
www.medrxiv.org/content/10.1...
www.medrxiv.org/content/10.1...
We turned to #Marchantia, which encodes only 3 Exo70 isoforms (Arabidopsis has 23!). Importantly this 3 still representa the key evolutionary branches of Exo70 tree.
October 31, 2025 at 10:19 AM
We turned to #Marchantia, which encodes only 3 Exo70 isoforms (Arabidopsis has 23!). Importantly this 3 still representa the key evolutionary branches of Exo70 tree.
Quest for Orthologs 8 meeting report/review: where AI, protein structure, isoforms & domains meet orthology. We review recent developments in the field, with applications from environmental genomics to agriculture. Many authors, led by @irenejulca.bsky.social. Open access: doi.org/10.1007/s002...
Quest for Orthologs in the era of Data Deluge and AI: Challenges and Innovations in Orthology Prediction and Data Integration - Journal of Molecular Evolution
The rapid advancement of DNA sequencing technologies and computational algorithms has led to an unprecedented surge in genomic data, driven by several large-scale sequencing projects worldwide. Orthol...
doi.org
October 23, 2025 at 6:22 AM
Quest for Orthologs 8 meeting report/review: where AI, protein structure, isoforms & domains meet orthology. We review recent developments in the field, with applications from environmental genomics to agriculture. Many authors, led by @irenejulca.bsky.social. Open access: doi.org/10.1007/s002...
Now: Carlos Fernado Buen Abad Najar: Identification of unannotated mRNA isoforms driving gene regulation and disease from large-scale RNA-seq data #ASHG25 🧪🧬🖥️
October 16, 2025 at 9:18 PM
Now: Carlos Fernado Buen Abad Najar: Identification of unannotated mRNA isoforms driving gene regulation and disease from large-scale RNA-seq data #ASHG25 🧪🧬🖥️
Great discussions at our #ASHG25 CoLab on how #PacBio HiFi multiomics connects genomes, transcriptomes, and proteomes.
Attendees explored how long-read sequencing reveals links between genetic variation, isoforms, and protein diversity in human cell types and disease pathways.
Attendees explored how long-read sequencing reveals links between genetic variation, isoforms, and protein diversity in human cell types and disease pathways.
October 16, 2025 at 7:00 PM
The latest #AlphaFold DB update is out!
We synchronised with UniProt release 2025_03, predicted protein isoforms across all species, and provide MSAs used to generate each prediction.
Proud of the team at the PDBe for the hard work that went into this. Grateful to play my part in it!
We synchronised with UniProt release 2025_03, predicted protein isoforms across all species, and provide MSAs used to generate each prediction.
Proud of the team at the PDBe for the hard work that went into this. Grateful to play my part in it!
We’re renewing our collaboration with Google DeepMind!
We'll keep developing the AlphaFold Database to support protein science worldwide 🎉
To mark the moment we’ve synchronised the database with UniProtKB release 2025_03.
www.ebi.ac.uk/about/news/t...
🖥️🧬 #AlphaFold
@pdbeurope.bsky.social
We'll keep developing the AlphaFold Database to support protein science worldwide 🎉
To mark the moment we’ve synchronised the database with UniProtKB release 2025_03.
www.ebi.ac.uk/about/news/t...
🖥️🧬 #AlphaFold
@pdbeurope.bsky.social
October 7, 2025 at 2:40 PM
The latest #AlphaFold DB update is out!
We synchronised with UniProt release 2025_03, predicted protein isoforms across all species, and provide MSAs used to generate each prediction.
Proud of the team at the PDBe for the hard work that went into this. Grateful to play my part in it!
We synchronised with UniProt release 2025_03, predicted protein isoforms across all species, and provide MSAs used to generate each prediction.
Proud of the team at the PDBe for the hard work that went into this. Grateful to play my part in it!
Join our second #ASHG25 CoLab at 2:30pm in CoLab Theater 2!
Explore how #PacBio HiFi multiomics connects genomes, transcriptomes, and proteomes to reveal links between genetic variation, isoforms, and protein diversity.
Full program here: bit.ly/4nmBnfn
Explore how #PacBio HiFi multiomics connects genomes, transcriptomes, and proteomes to reveal links between genetic variation, isoforms, and protein diversity.
Full program here: bit.ly/4nmBnfn
October 6, 2025 at 9:06 PM
Join our second #ASHG25 CoLab at 2:30pm in CoLab Theater 2!
Explore how #PacBio HiFi multiomics connects genomes, transcriptomes, and proteomes to reveal links between genetic variation, isoforms, and protein diversity.
Full program here: bit.ly/4nmBnfn
Explore how #PacBio HiFi multiomics connects genomes, transcriptomes, and proteomes to reveal links between genetic variation, isoforms, and protein diversity.
Full program here: bit.ly/4nmBnfn
🧪Happy to share our latest paper in Genome Biology.
We profiled #RNA isoforms from 31 neuropsychiatric risk genes in the human brain using long-read sequencing. Unannotated isoforms commonly made up a significant proportion of a gene's expression.
genomebiology.biomedcentral.com/articles/10....
We profiled #RNA isoforms from 31 neuropsychiatric risk genes in the human brain using long-read sequencing. Unannotated isoforms commonly made up a significant proportion of a gene's expression.
genomebiology.biomedcentral.com/articles/10....
Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain - Genome Biology
Background Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or RNA isoforms made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Results Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profile the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in Human brain. We show most risk genes are more complex than previously reported, identifying 363 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity is detected in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirms translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in the brain. Conclusions Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in the human brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of candidate neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.
genomebiology.biomedcentral.com
October 3, 2025 at 4:18 AM
🧪Happy to share our latest paper in Genome Biology.
We profiled #RNA isoforms from 31 neuropsychiatric risk genes in the human brain using long-read sequencing. Unannotated isoforms commonly made up a significant proportion of a gene's expression.
genomebiology.biomedcentral.com/articles/10....
We profiled #RNA isoforms from 31 neuropsychiatric risk genes in the human brain using long-read sequencing. Unannotated isoforms commonly made up a significant proportion of a gene's expression.
genomebiology.biomedcentral.com/articles/10....
The #Drosophila Dscam1 gene generates 10000s of isoforms, but only a small fraction supports neuronal functions. This study shows that #fitness & #immunity are the likely primary evolutionary drivers of Dscam1 isoform diversity in #arthropods @plosbiology.org 🧪 plos.io/4gp8cWd
September 15, 2025 at 5:15 PM
The #Drosophila Dscam1 gene generates 10000s of isoforms, but only a small fraction supports neuronal functions. This study shows that #fitness & #immunity are the likely primary evolutionary drivers of Dscam1 isoform diversity in #arthropods @plosbiology.org 🧪 plos.io/4gp8cWd
The #Drosophila Dscam1 gene generates 10000s of isoforms, but only a small fraction supports neuronal functions. This study shows that #fitness & #immunity are the likely primary evolutionary drivers of Dscam1 isoform diversity in #arthropods @plosbiology.org 🧪 plos.io/4gp8cWd
September 15, 2025 at 8:44 AM
The #Drosophila Dscam1 gene generates 10000s of isoforms, but only a small fraction supports neuronal functions. This study shows that #fitness & #immunity are the likely primary evolutionary drivers of Dscam1 isoform diversity in #arthropods @plosbiology.org 🧪 plos.io/4gp8cWd
6/ Still, p30 binds chromatin and is transcriptionally active — so why the defective inflammatory response?
ChIP-seq of both isoforms showed similar binding on inflammatory genes. Was there something else?
ChIP-seq of both isoforms showed similar binding on inflammatory genes. Was there something else?
April 14, 2025 at 1:33 PM
6/ Still, p30 binds chromatin and is transcriptionally active — so why the defective inflammatory response?
ChIP-seq of both isoforms showed similar binding on inflammatory genes. Was there something else?
ChIP-seq of both isoforms showed similar binding on inflammatory genes. Was there something else?
Have you ever been #sleep deprived? This is how brain cells and different isoforms of transcripts do in just 5 hours ! (in mice) #SingleCell #transcriptomics www.cell.com/iscience/ful...
A global transcriptional atlas of the effect of acute sleep deprivation in the mouse frontal cortex
Molecular biology; Neuroscience; Molecular neuroscience; Omics; Transcriptomics
www.cell.com
November 14, 2024 at 5:34 AM
Have you ever been #sleep deprived? This is how brain cells and different isoforms of transcripts do in just 5 hours ! (in mice) #SingleCell #transcriptomics www.cell.com/iscience/ful...
Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy https://www.biorxiv.org/content/10.1101/2024.04.24.590768v1
Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy https://www.biorxiv.org/content/10.1101/2024.04.24.590768v1
Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characteris
www.biorxiv.org
April 25, 2024 at 3:22 AM
Dual CRALBP isoforms unveiled: iPSC-derived retinal modelling and AAV2/5-RLBP1 gene transfer raise considerations for effective therapy https://www.biorxiv.org/content/10.1101/2024.04.24.590768v1
Alternative splicing (AS) is common, but its impact on the proteome remains debated, especially in primary cells.
What determines which AS isoforms result in abundant proteins ?
We find that proteoform-specific ...
🧵
www.biorxiv.org/content/10.1...
What determines which AS isoforms result in abundant proteins ?
We find that proteoform-specific ...
🧵
www.biorxiv.org/content/10.1...
April 28, 2025 at 10:28 AM
Alternative splicing (AS) is common, but its impact on the proteome remains debated, especially in primary cells.
What determines which AS isoforms result in abundant proteins ?
We find that proteoform-specific ...
🧵
www.biorxiv.org/content/10.1...
What determines which AS isoforms result in abundant proteins ?
We find that proteoform-specific ...
🧵
www.biorxiv.org/content/10.1...
3) Overall we annotated ~70% more transcript isoforms than our recent annotation of GRCz11.
4) Most of the increase is for additional isoforms of protein-coding genes, but the lncRNA count did increase from 8740 in the RS_2024_08 annotation of GRCz11 to 12,861 in GRCz12.
4) Most of the increase is for additional isoforms of protein-coding genes, but the lncRNA count did increase from 8740 in the RS_2024_08 annotation of GRCz11 to 12,861 in GRCz12.
May 15, 2025 at 4:23 PM
3) Overall we annotated ~70% more transcript isoforms than our recent annotation of GRCz11.
4) Most of the increase is for additional isoforms of protein-coding genes, but the lncRNA count did increase from 8740 in the RS_2024_08 annotation of GRCz11 to 12,861 in GRCz12.
4) Most of the increase is for additional isoforms of protein-coding genes, but the lncRNA count did increase from 8740 in the RS_2024_08 annotation of GRCz11 to 12,861 in GRCz12.
Ophthopedia Update: Differential Expression Profiles of MAPT (TAU ) Gene Isoforms in Dry Age-Related Macular Degeneration: Publication date: Available online 11 July 2025
Source: Experimental Eye Research
Author(s): Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila…
Source: Experimental Eye Research
Author(s): Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila…
Differential Expression Profiles of MAPT (TAU ) Gene Isoforms in Dry Age-Related Macular Degeneration
Publication date: Available online 11 July 2025
Source: Experimental Eye Research
Author(s): Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila Soheili, Fatemeh Suri
dlvr.it
July 11, 2025 at 12:39 PM
Ophthopedia Update: Differential Expression Profiles of MAPT (TAU ) Gene Isoforms in Dry Age-Related Macular Degeneration: Publication date: Available online 11 July 2025
Source: Experimental Eye Research
Author(s): Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila…
Source: Experimental Eye Research
Author(s): Shermin Lak, Mozhgan Rezaei Kanavi, Kia Bayat, Hamid Ahmadieh, Zahra-Soheila…
🧬 Cracking the genetic code of Epstein-Barr virus! 1,453 transcript isoforms reveal mind-blowing viral gene expression secrets. 🦠 Potential game-changer for future therapies! #Genomics #ViralResearch #ScienceBreakthrough https://emmecola.github.io/genomics-daily
July 11, 2025 at 6:36 AM
🧬 Cracking the genetic code of Epstein-Barr virus! 1,453 transcript isoforms reveal mind-blowing viral gene expression secrets. 🦠 Potential game-changer for future therapies! #Genomics #ViralResearch #ScienceBreakthrough https://emmecola.github.io/genomics-daily
Signal peptides as potential structural modulators of human splice isoforms www.biorxiv.org/cont...
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#proteomics #prot-preprint
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#proteomics #prot-preprint
June 1, 2025 at 4:40 PM
Signal peptides as potential structural modulators of human splice isoforms www.biorxiv.org/cont...
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#proteomics #prot-preprint
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#proteomics #prot-preprint
Antagonistic and Synergistic Roles of Tomato AFP3 Isoforms in Hormonal Regulation and Development https://www.biorxiv.org/content/10.1101/2025.06.18.660365v1
June 23, 2025 at 2:01 PM
Antagonistic and Synergistic Roles of Tomato AFP3 Isoforms in Hormonal Regulation and Development https://www.biorxiv.org/content/10.1101/2025.06.18.660365v1
Fm Rafi Ahmed et al:
'In this study, we show that human virus specific effector CD8 T cells reexpress the CD45RA isoforms after antigen clearance and consequently, functional memory CD8 T cells generated after an acute viral infection or mRNA vaccination express CD45RA'
www.pnas.org/doi/10.1073/...
'In this study, we show that human virus specific effector CD8 T cells reexpress the CD45RA isoforms after antigen clearance and consequently, functional memory CD8 T cells generated after an acute viral infection or mRNA vaccination express CD45RA'
www.pnas.org/doi/10.1073/...
August 7, 2025 at 7:17 AM
Fm Rafi Ahmed et al:
'In this study, we show that human virus specific effector CD8 T cells reexpress the CD45RA isoforms after antigen clearance and consequently, functional memory CD8 T cells generated after an acute viral infection or mRNA vaccination express CD45RA'
www.pnas.org/doi/10.1073/...
'In this study, we show that human virus specific effector CD8 T cells reexpress the CD45RA isoforms after antigen clearance and consequently, functional memory CD8 T cells generated after an acute viral infection or mRNA vaccination express CD45RA'
www.pnas.org/doi/10.1073/...
🚀 Stop missing the full transcript story!
New research combines @10xgenomics.bsky.social Chromium Single Cell + long-read sequencing:
🔬Thousands of unannotated isoforms discovered
📊Cell-type specific splicing patterns revealed
🎯Complete transcript characterization achieved
#SingleCellRNA #LongRead
New research combines @10xgenomics.bsky.social Chromium Single Cell + long-read sequencing:
🔬Thousands of unannotated isoforms discovered
📊Cell-type specific splicing patterns revealed
🎯Complete transcript characterization achieved
#SingleCellRNA #LongRead
September 12, 2025 at 3:43 AM
🚀 Stop missing the full transcript story!
New research combines @10xgenomics.bsky.social Chromium Single Cell + long-read sequencing:
🔬Thousands of unannotated isoforms discovered
📊Cell-type specific splicing patterns revealed
🎯Complete transcript characterization achieved
#SingleCellRNA #LongRead
New research combines @10xgenomics.bsky.social Chromium Single Cell + long-read sequencing:
🔬Thousands of unannotated isoforms discovered
📊Cell-type specific splicing patterns revealed
🎯Complete transcript characterization achieved
#SingleCellRNA #LongRead
Very happy to present my work on 1q21 disorder and myomegalin isoforms in neural development at the #cshl2024brain Please come by Poster #77
December 10, 2024 at 2:01 PM
Very happy to present my work on 1q21 disorder and myomegalin isoforms in neural development at the #cshl2024brain Please come by Poster #77
A human commons cell atlas reveals cell type specificity for OAS1 isoforms https://www.biorxiv.org/content/10.1101/2024.03.23.586412v1
A human commons cell atlas reveals cell type specificity for OAS1 isoforms https://www.biorxiv.org/content/10.1101/2024.03.23.586412v1
We describe an open source Human Commons Cell Atlas comprising 2.9 million cells across 27 tissues t
www.biorxiv.org
March 25, 2024 at 2:46 AM
A human commons cell atlas reveals cell type specificity for OAS1 isoforms https://www.biorxiv.org/content/10.1101/2024.03.23.586412v1