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Research article
Xusheng Wang
University of North Dakota
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1759-9588
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6J (B6) and DBA/2J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology.
Results
By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and identified four common inheritance patterns, including 1,133 dominant, 980 additive, 63 over- and 62 under-dominant expression. We further applied the proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis‐effects and 17 variant peptides showing trans‐effects. Comparison of regulation at transcript and protein levels show a significant divergence.
Conclusions
The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans‐acting regulatory differences to protein expression.
Keywords
Proteome, Mouse, Brain, Protein expression, Expression pattern, Protein regulation
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Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- ARRIVEChecklistv3.pdf
ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments)
- additionalfile1.xlsx
Supplementary tables S1-S7. Supplementary Table S1: Proteins identified and quantified by LC/LC-MS/MS. Supplementary Table S2: Differentially expressed (DE) proteins in whole brain between B6 and D2 strains. Supplementary Table S3: Significantly enriched Gene Ontology (GO) terms of DE proteins between C57BL/6J and DBA/2J. Supplementary Table S4: Inheritance patterns detected by protein co-expression network analysis. Supplementary Table S5: Significantly enriched Gene Ontology (GO) terms of proteins with different inheritance patterns. Supplementary Table S6: Variant peptides detected by the proteogenomics analysis. Supplementary Table S7: Peptides showing allele-specific expression.
- additionalfile2.pdf
Supplementary figures S1-S3. Supplementary Figure S1. Scatter plots showing correlation analysis of two replicates of mouse samples. R2 is the coefficient of determination. Supplementary Figure S2. Heatmap showing differentially expressed proteins between four groups. Supplementary Figure S3. Enrichment analysis of proteins with additive and dominant inheritances.
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CURRENT STATUS: Published
View the published article at BMC Genomics.
Version 1
Posted 14 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 13 Jul, 2021
Review #2 received
Received 12 Jul, 2021
Reviewer #2 agreed
On 28 Jun, 2021
Review #1 received
Received 18 Jun, 2021
Reviewer #1 agreed
On 09 Jun, 2021
Editor assigned
On 06 Jun, 2021
Reviewers invited
Invitations sent on 06 Jun, 2021
Submission checks complete
On 06 Jun, 2021
Editor invited
On 06 Jun, 2021
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On 14 May, 2021
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Subject Areas
Epigenetics & Genomics
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A new preprint design is coming!
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See the published version of this preprint at BMC Genomics.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Xusheng Wang
University of North Dakota
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1759-9588
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Genomics.
Version 1
Posted 14 Jun, 2021
No community comments so far
Editorial decision: Major revision
On 13 Jul, 2021
Review #2 received
Received 12 Jul, 2021
Reviewer #2 agreed
On 28 Jun, 2021
Review #1 received
Received 18 Jun, 2021
Reviewer #1 agreed
On 09 Jun, 2021
Editor assigned
On 06 Jun, 2021
Reviewers invited
Invitations sent on 06 Jun, 2021
Submission checks complete
On 06 Jun, 2021
Editor invited
On 06 Jun, 2021
First submitted
On 14 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Genomics.
Background
Natural variation in protein expression is common in all organisms and contributes to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6J (B6) and DBA/2J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology.
Results
By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and identified four common inheritance patterns, including 1,133 dominant, 980 additive, 63 over- and 62 under-dominant expression. We further applied the proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE), identifying 33 variant peptides with cis‐effects and 17 variant peptides showing trans‐effects. Comparison of regulation at transcript and protein levels show a significant divergence.
Conclusions
The results provide a comprehensive analysis of genetic architecture of protein expression and the contribution of cis- and trans‐acting regulatory differences to protein expression.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- ARRIVEChecklistv3.pdf
ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments)
- additionalfile1.xlsx
Supplementary tables S1-S7. Supplementary Table S1: Proteins identified and quantified by LC/LC-MS/MS. Supplementary Table S2: Differentially expressed (DE) proteins in whole brain between B6 and D2 strains. Supplementary Table S3: Significantly enriched Gene Ontology (GO) terms of DE proteins between C57BL/6J and DBA/2J. Supplementary Table S4: Inheritance patterns detected by protein co-expression network analysis. Supplementary Table S5: Significantly enriched Gene Ontology (GO) terms of proteins with different inheritance patterns. Supplementary Table S6: Variant peptides detected by the proteogenomics analysis. Supplementary Table S7: Peptides showing allele-specific expression.
- additionalfile2.pdf
Supplementary figures S1-S3. Supplementary Figure S1. Scatter plots showing correlation analysis of two replicates of mouse samples. R2 is the coefficient of determination. Supplementary Figure S2. Heatmap showing differentially expressed proteins between four groups. Supplementary Figure S3. Enrichment analysis of proteins with additive and dominant inheritances.
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