Blood Protein - Methods summary

Summary

The Blood Proteins resource contains information regarding the proteins present in blood. Externally and “In-house” generated data are integrated to explore human plasma protein profiles in healthy individuals. Plasma levels in blood are presented, based both on antibody-based immune assays and mass spectrometry-based proteomics.

Key publications

Uhlén M et al. (2019) “The human secretome” Sci signal

What can you learn from the Blood Protein section?

Learn about

  • concentration of human plasma proteins based on immune assays and MS
  • expression of plasma proteins in healthy individuals based on PEA

Data overview

Data type Count Data Coverage (nr genes)
Protein concentration Protein concentrations across 501 genes measured in Immunoassays 501
Protein concentration Protein concentrations across 4285 genes measured with mass spectrometry 4285


How has the data been generated?

Plasma proteins were measured with the proximity extension assay (Olink Explore HT, 5,416 protein targets) in two longitudinal cohorts of healthy individuals:

  • Wellness: 96 individuals aged 50-65 (50% women) from the SCAPIS Wellness Profiling program, sampled at six visits over two years (561 samples).
  • BAMSE: 100 individuals (50 males, 50 females) from the Swedish birth cohort BAMSE, sampled at ages 4, 8, 16 and 24 (400 samples).

All samples were EDTA plasma. Data were normalized by the provider and reported as Normalized Protein eXpression (NPX), a relative unit on a log2 scale. Values flagged with QC warnings were excluded, as were samples with more than 50% QC warnings. APOE and the proteins in dilution block 8 (n = 68, the most abundant proteins) were excluded for technical reasons.

The Blood Atlas also contain information of proteins detected by mass spectrometry-based proteomics, based on publicly available data on the Peptide Atlas. The mass-spectrometry based data was filtered to include only the minimal, non-redundant list of proteins derived from the set of identified peptides and exclude entries labelled as contaminants. In addition, the concentration of actively secreted proteins was annotated using publicly available literature.


Mixed-effects models

For each protein and cohort, a linear mixed-effects model was fitted with age and sex as fixed effects and a random intercept per individual. Proteins with more than 80% of samples below the limit of detection (LOD) in a cohort were excluded from that cohort’s analysis. The proportion of variance explained by age and sex (marginal R²), and by the individual (conditional R² minus marginal R²), was estimated with Nakagawa’s R². For proteins with a singular fit, the variance attributed to the individual was set to zero. P-values for the age and sex effects were adjusted with the Benjamini–Hochberg method, and effects with an adjusted p < 0.05 were considered significant.

What is presented in the section?

In the gene summary page of the Blood Proteins section, the protein levels from the PEA based assays are shown. The longitudinal variation in the expression of a protein in plasma from healthy individuals is displayed in two line plots separated according to sex.



In addition, the gene summary page include the blood concentrations from mass spectrometry studies when available in the Peptide Atlas. The predicted concentration in blood (plasma or serum) is shown.


Furthermore, the blood concentration for the proteins annotated to be secreted to blood is shown (when available). The reported concentration in blood are shown for some representative studies with reference to the literature.


Data tables

Detailed tables for plasma concentrations meansured by differetn techniques.

Immunoassay-based plasma concentrations

Table 1. Concentrations for proteins secreted to blood. Measured by immunoassays.

Gene Gene description Mean concentration Reference
ALB Albumin 42 g/L 45 g/L
43 g/L
40 g/L
FGB Fibrinogen beta chain 3.3 g/L 3.3 g/L
3.3 g/L
TF Transferrin 2.7 g/L 3.1 g/L
2.6 g/L
2.5 g/L
A2M Alpha-2-macroglobulin 1.6 g/L 2.9 g/L
1.7 g/L
1.0 g/L
950 mg/L
SERPINA1 Serpin family A member 1 1.9 g/L 3.1 g/L
2.3 g/L
1.9 g/L
1.6 g/L
1.4 g/L
1.3 g/L
APOA1 Apolipoprotein A1 1.5 g/L 3.0 g/L
1.6 g/L
1.4 g/L
1.4 g/L
740 mg/L
700 mg/L
AHSG Alpha 2-HS glycoprotein 860 mg/L 1.3 g/L
1.1 g/L
230 mg/L
C3 Complement C3 1.3 g/L 1.7 g/L
1.6 g/L
1.3 g/L
1.2 g/L
1.2 g/L
920 mg/L
HP Haptoglobin 1.5 g/L 2.4 g/L
1.6 g/L
1.3 g/L
1.2 g/L
1.2 g/L
ORM1 Orosomucoid 1 770 mg/L 880 mg/L
870 mg/L
730 mg/L
610 mg/L
HPX Hemopexin 640 mg/L 750 mg/L
610 mg/L
600 mg/L
590 mg/L
APOB Apolipoprotein B 1.3 g/L 1.9 g/L
1.9 g/L
1.5 g/L
1.1 g/L
940 mg/L
720 mg/L
CFH Complement factor H 400 mg/L 640 mg/L
290 mg/L
260 mg/L
VTN Vitronectin 750 mg/L 1.4 g/L
930 mg/L
340 mg/L
320 mg/L
SERPINA3 Serpin family A member 3 700 mg/L 1.1 g/L
330 mg/L
CP Ceruloplasmin 240 mg/L 300 mg/L
220 mg/L
190 mg/L
APOA2 Apolipoprotein A2 110 mg/L 300 mg/L
160 mg/L
490 µg/L
360 µg/L
FN1 Fibronectin 1 260 mg/L 290 mg/L
230 mg/L
C4B Complement C4B (Chido blood group) 280 mg/L 300 mg/L
290 mg/L
280 mg/L
230 mg/L
APOH Apolipoprotein H 250 mg/L 290 mg/L
280 mg/L
170 mg/L
CLU Clusterin 170 mg/L 270 mg/L
240 mg/L
180 mg/L
110 mg/L
41 mg/L
C4BPB Complement component 4 binding protein beta 230 mg/L 270 mg/L
210 mg/L
210 mg/L
TTR Transthyretin 290 mg/L 310 mg/L
290 mg/L
260 mg/L
FGG Fibrinogen gamma chain 270 mg/L 300 mg/L
290 mg/L
250 mg/L
230 mg/L
CRISPLD2 Cysteine rich secretory protein LCCL domain containing 2 220 mg/L 220 mg/L
C1QC Complement C1q C chain 150 mg/L 180 mg/L
140 mg/L
140 mg/L
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Mass spectrometry-based plasma concentrations

Table 2. A list of the proteins detected in blood by mass spectrometry.

Gene Gene description Concentration
A2M Alpha-2-macroglobulin 420 mg/L
C3 Complement C3 370 mg/L
HPX Hemopexin 270 mg/L
HP Haptoglobin 260 mg/L
APOB Apolipoprotein B 250 mg/L
TF Transferrin 250 mg/L
CP Ceruloplasmin 240 mg/L
SERPINA1 Serpin family A member 1 230 mg/L
C4B Complement C4B (Chido blood group) 230 mg/L
C4A Complement C4A (Rodgers blood group) 230 mg/L
FGA Fibrinogen alpha chain 210 mg/L
FGB Fibrinogen beta chain 170 mg/L
APOA1 Apolipoprotein A1 160 mg/L
CFH Complement factor H 130 mg/L
FGG Fibrinogen gamma chain 130 mg/L
SERPINA3 Serpin family A member 3 130 mg/L
ITIH1 Inter-alpha-trypsin inhibitor heavy chain 1 110 mg/L
AHSG Alpha 2-HS glycoprotein 110 mg/L
GC GC vitamin D binding protein 110 mg/L
ITIH4 Inter-alpha-trypsin inhibitor heavy chain 4 98 mg/L
CFB Complement factor B 89 mg/L
A1BG Alpha-1-B glycoprotein 88 mg/L
FN1 Fibronectin 1 84 mg/L
HPR Haptoglobin-related protein 83 mg/L
SERPINC1 Serpin family C member 1 76 mg/L
PLG Plasminogen 72 mg/L
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