CSF Sample Preparation, Itraq Labelling, LCMSMS Setup and Proteinpilot Processing
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SUPPLEMENTARY INFORMATION
CSF sample preparation, iTRAQ labelling, LCMSMS setup and ProteinPilot Processing CSF proteins (50g for each of the 8 samples, concentrations determined by BCA assay) were diluted (50mM NaHCO3) so that all had equal total protein concentration. For subsequent steps the iTRAQ reagents protocol (Applied Biosystems, Foster City, CA) was followed, except that iodoacetamide (4mM) was used to alkylate cysteines, and immediately prior to adding iTRAQ reagents, Na2CO3 (500mM) was added (1 L) to ensure a basic pH (ca 8.5). Following off-line strong cation exchange the labeled peptides were dried under vacuum and an off-line C18 sample clean-up step was performed (Peptide MacroTrap, Michrom Bioresources, Auburn, CA), eluting with 500L CH3CN:water:formic acid (50:50:0.1, v:v:v), followed by 200L neat CH3CN. A portion of the labeled sample (ca 10%) was dried under vacuum and resuspended in water:formic acid:HFBA (99:1:0.05, v:v:v). 2D LCMSMS mass spectrometry was performed on an API QStar Elite hybrid tandem mass spectrometer (Applied Biosystems, Foster City, CA). Peptides (3-5g total load) were initially captured onto a SCX micro column (0.75 x ~20mm, Poros S10, Applied Biosystems) and the eluant from multiple salt elution steps (unbound load, 5, 10, 15, 20, 25, 30, 40, 50, 100, 250, 500 and 1000 mM ammonium acetate) captured and desalted on a C18 precolumn cartridge (500 m × 2 mm, Michrom Bioresources). After a 10 min wash the pre- column was switched (Switchos) into line with a fritless analytical column (75 µm x ~12 cm) containing C18 reverse phase packing material (Magic, 5 μ, 200Å) (Gatlin et al 1998). Peptides were eluted using a linear gradient of buffer A to H2O:CH3CN (50:50, 0.1 % formic acid-buffer B) at ~300 nl/min over 90 min. High voltage (2300 V) was applied through a low volume tee (Upchurch Scientific) at the column inlet and the outlet positioned ~ 1 cm from the orifice of an API QStar Elite hybrid tandem mass spectrometer (Applied Biosystems, Foster City CA). Positive ions were generated by electrospray and the QStar operated in information dependent acquisition mode (IDA). A Tof MS survey scan was acquired (m/z 350-1700, 0.75 s) and the 3 largest multiply charged ions (counts > 20, charge state 2 and 4) sequentially selected by Q1 for MS-MS analysis. Nitrogen was used as collision gas and an optimum collision energy automatically chosen (based on charge state and mass). Tandem mass spectra were accumulated for up to 2.5 s (m/z 65-2000) with 2 repeats. Automated online 2D LC/MS/MS was carried out (7 technical replicates) and the combined data processed using ProteinPilot software 3.0.0 (ABSciex) using the ipi.HUMAN.v3.58 protein database. A p value of < 0.05 was used as the cutoff for accepting statistically significant changes in protein expression level. SI Table 1 DAVID v6.7 software used to determine biological function enrichment of the proteins significantly dysregulated in the CSF of subjects with mild or moderate delirium relative to the mild AD control with no delirium. All delirium subjects from both the Sydney and Edinburgh studies are represented here. The proteins used for DAVID analysis are a subset of those listed in SI Table 4 (supplementary information), and are dysregulated in at least 4 out of 17 patients with delirium. The same protein set as used in the STRING network analysis shown in figure 2A. The background list used for this DAVID analysis was the full homo sapiens protein list. Medium classification stringency was used.
Biological function (most Enrichment No. proteins Benjamini FDR score significant annotation cluster Score of the in this group score category, based on FDR score) cluster Secreted 24.8 32 4.3E-29 7.2E-28 (SP_PIR_KEYWORDS) Plasma (SP_PIR_KEYWORDS) 21.11 19 5.0E-32 4.2E-31 Response to wounding 9.24 15 3.7E-10 6.4E-10 (GOTERM_BP_FAT) Endopeptidase inhibitory 5.86 9 7.5E-8 7.9E-7 activity (GOTERM_MF_FAT) Secretory granule 5.73 10 1.3E-8 5.7E-7 (GOTERM_CC_FAT) Amyloid 5.45 5 1.2E-6 1.0E-4 (SP_PIR_KEYWORDS) Regulation of response to 4.62 9 external stimulus 2.3E-7 1.2E-6 (GOTERM_BP_FAT) Wound healing 4.3 9 7.5E-7 5.2E-6 (GOTERM_BP_FAT) Heparin binding 4.16 5 1.2E-6 1.2E-4 (SP_PIR_KEYWORDS) Liver (SP_PIR_KEYWORDS) 2.96 7 1.2E-8 7.9E-7 Acute-phase response 2.88 6 2.9E-6 2.5E-5 (GOTERM_BP_FAT) High-density lipoprotein 2.72 6 particle 5.5E-8 4.8E-6 (GOTERM_CC_FAT) Regeneration 2.69 5 6.5E-4 1.8E-2 (GOTERM_BP_FAT) Protease inhibitor 2.36 5 2.4E-4 3.9E-2 (SP_PIR_KEYWORDS) Response to inorganic 1.78 6 2.7E-3 8.8E-2 substance (GOTERM_BP_FAT) SI Table 2 Design of the three iTRAQ experiments; each line represents an individual subject unless otherwise stated. Subjects have one of the following ; moderate to severe delirium, mild delirium, moderate AD with no delirium (neurological comparison group; Sydney Study only), mild AD with no delirium (control group; Sydney Study only) and normal controls (Edinburgh Study only). The 17 delirium subjects were assayed individually. The 17 AD subjects (Sydney Study) and the 8 normal controls (Edinburgh Study) were assayed in four pooled CSF groups (4-5 subjects in each pooled group), to allow for the 8-plex format in each of three 8-plex iTRAQ experiments (Expt 1, Expt 2 and Expt 3).
Subject # and diagnosis Age Sex Delirium index MMSE score Delirium Subsequent Total protein (iTRAQ tag and Expt #) (years) M/F score (DI)2 duration days of (BCA assay) Pre-LP (days) delirium mg/mL neat CSF3 Sydney Delirium Study (iTRAQ experiments 1 and 2) 1 mod/sev delirium (113 Expt 1) 88 M 20 14 5 >10 1.23 27 mod/sev delirium (114 Expt 1) 85 M 21 18 17 >10 1.27 41 mod/sev delirium (115 Expt 1) 66 F 20 Missing 24 1 0.58 24 mild delirium (116 Expt 1) 66 M 11 Missing 30 >10 1.91 26 mild delirium (117 Expt 1) 73 M 11 21 40 >10 0.87 35 mild delirium (118 Expt 1) 82 M 9 15 6 1 0.47 32 mild AD (119 Expt 1) 1 95 F 3 25 0 0.42 0.88 34 83 M 4 24 0 .0.57 36 86 F 1 26 0 0.72 45 68 F 1 25 0 0.26 31 moderate AD (121 Expt 1) 1 79 M 6 14 0 0.89 39 84 M 1 12 0 0.49 42 84 M 3 21 0 0.49 44 85 M 3 20 0 0.36 38 mod/sev delirium (113 Expt 2) 93 F 13 12 5 1 0.31 46 mod/sev delirium (114 Expt 2) 81 M 19 9 8 >10 0.22 53 mod/sev delirium (115 Expt 2) 88 F 19 Missing 5 >10 0.71 25 mild delirium (116 Expt 2) 77 M 12 13 5 4* 0.17 67 mild delirium (117 Expt 2) 90 M 8 23 17 4 0.35 47 mild delirium (118 Expt 2) 75 F 12 15 12 >10 0.16 68 mild AD (119 Expt 2) 1,4 88 F 3 22 0 0 0.56 43 87 F 3 22 0 0 0.63 49 79 F 3 26 0 0 0.60 52 82 F 3 22 0 0 0.22 55 moderate AD (121 Expt 2) 1 84 F 4 12 0 0 0.32 72 81 F 5 11 0 0 0.33 48 73 F 3 18 0 0 0.44 50 81 F 4 19 0 0 0.26 74 82 M 4 19 0 0 0.35 Edinburgh Delirium Study 4 Age Sex Pre-Op DRS- Pre-op Delirium Subsequent Total protein (iTRAQ experiment 3) (years) M/F R985 (Post-Op MMSE score duration days of (BCA assay) DRS-(98) (post-op Pre-Op (days) delirium Post- mg/mL neat MMSE) Op CSF3 C060 Moderate delirium (113) 89 M 18 (33) 22 (4) 1-2 days >7 0.95 C075 Moderate delirium (114) 91 F 18 (22) 15 (14) 1-2 days 1 1.26 C087 Moderate delirium (115) 86 M 19 (18) 23 (24) 1-2 days 1 0.64 C073 Mild delirium (116) 86 F 6 (17) 28 (27) 0 3 1.71 C085 Mild delirium (117) 66 F 11 (8) 25 (29) 1-2 days 2 0.80 C001 Low normal (118) 1 78 F 1 (4) 30 (28) 0 0 0.82 C023 89 F 8 (9) 28 (29) 0 0 0.80 C026 78 F 8 (6) 27 (29) 0 0 0.81 C079 63 F 6 (3) 26 (26) 0 0 0.68 C010 High normal (121) 1 87 M 2 (6) 29 (25) 0 0 1.20 C020 70 F 5 (6) 27 (25) 0 0 0.52 C039 95 F 4 (4) 25 (28) 0 0 0.91 C077 89 F 4 (4) 27 (25) 0 0 0.86 *=discharged with delirium >10= CAM done daily for 10 days after LP and still positive at that time 1 These samples represent pooled CSF from 4-5 subjects each, however details are provided for individual subjects within the pooled group. The Edinburgh normal control group was divided into “low normal” and “high normal” based on a combination of clinical observation and test results. The “low normal” group of C001, C023, C026 and C079 developed mild subsyndromal delirium as they satisfied one or two DSM IV criteria peri-operatively, and 3/4 had inattention at some point. The “high normal” group of C010, C020, C039 and C077 did not have subsyndromal delirium. 2 DI score is based on the method of McCusker J, et al 2004. 3 CSF protein concentration can vary considerably and values from 0.21-2.74mg/mL has been reported (Williams, K. M. & Marshall 2001) 4 In the Edinburgh experiment, iTRAQ tag 119 was the Sydney Delirium Study mild AD (119 Expt 2) sample, chosen so that a cross-study comparison could be made. 5 DRS is the Delirium Rating Scale-Revised ‘98 (Trzepacz et al 2001). 6A modified version of the APACHE II score was used in the Edinburgh study, omitting arterial pH, since arterial blood sampling is not routinely performed peri-operatively in patients with hip fracture
References Gatlin, C. L., Kleemann, G. R., Hays, L. G., Link, A. J. & Yates, J. R., 3rd. Protein identification at the low femtomole level from silver-stained gels using a new fritless electrospray interface for liquid chromatography-microspray and nanospray mass spectrometry. Anal Biochem 263, 93-101, doi:S0003-2697(98)92809-3 [pii]10.1006/abio.1998.2809 (1998).
McCusker, J., Cole, M. G., Dendukuri, N. & Belzile, E. The delirium index, a measure of the severity of delirium: new findings on reliability, validity, and responsiveness. J Am Geriatr Soc 52, 1744-1749, doi:10.1111/j.1532-5415.2004.52471.xJGS52471 [pii] (2004).
Williams, K. M. & Marshall, T. Protein concentration of cerebrospinal fluid by precipitation with Pyrogallol Red prior to sodium dodecyl sulphate-polyacrylamide gel electrophoresis. J Biochem Biophys Methods 47, 197-207, doi:S0165022X00001354 [pii] (2001).
Trzepacz PT, Mittal D, Torres R, Kanary K, Norton, J & Jimerson N. Validation of the Delirium Rating Scale-Revised-98: comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. J Neuropsychiatry Clin Neurosci; 13, 229–42, doi: 10.1176/appi.neuropsych.13.2.229 (2001). SI Table 3 Proteins dysregulated in delirium CSF relative to control CSF, based on two iTRAQ experiments, each with 7 technical replicates using the Sydney Delirium cohort. Yellow and green labels represent data from the first and second experiment respectively. Each experiment included 6 individuals with delirium (3 each of mild and moderate delirium) and two pooled AD groups (one moderate and the other mild AD, being the control group). Data was analysed using Protein Pilot v3.0.0, and using the ipi.HUMAN.v3.58 database. The iTRAQ reporter ion ratios relative to the 119 control ion are shown, with significantly upregulated proteins highlighted in pink and significantly downregulated proteins highlighted in blue (p ≤ 0.05), the boxes with no colour being non-significantly different. The proteins in this table are dysregulated in 50% or more of the subjects, and are a subset of the full group of dysregulated proteins shown in SI Table 4. All proteins were identified with high confidence (unused score of ≥ 1.3 represents ≥ 95% confidence in correct sequence identification). The % protein sequence coverage is in most instances >30% and all proteins were identified with at least two unique peptides, and in most instances > 20 peptides iTRAQ reporter ion ratios (all relative to 119 reporter = mild AD with no delirium control) moderate delirium mild delirium moerate AD Unused %Cov(95) Accession Name Peptides(95%) 113:119 114:119 115:119 116:119 117:119 118:119 121:119 36.34 40.30 884926.1 ORM1 alpha-1-acid glycoprotein 1 precursor 41 1.514 1.435 1.231 2.570 1.988 1.246 0.727 38.51 51.74 49 1.214 1.299 1.544 1.666 1.210 1.548 1.116 12.08 23.49 166729.4 AZGP1 Zinc-alpha-2-glycoprotein 5 0.913 1.120 0.936 1.107 0.823 1.013 0.782 22.06 38.26 12 1.154 1.268 1.454 1.121 1.434 1.254 1.202 157.69 52.56 783987.2 C3 Complement C3 (Fragment) 89 1.050 0.885 0.949 1.085 1.173 1.070 1.020 157.97 52.19 129 1.180 1.077 1.161 0.981 1.036 1.132 1.057 121.09 73.21 22463.1 TF Serotransferrin 128 1.008 0.996 1.187 0.737 0.868 0.967 0.941
s 109.61 65.76 127 1.209 1.659 1.614 1.293 1.452 1.000 1.041 t
n 87.06 68.42 553177.1 SERPINA1 Isoform 1 of Alpha-1-antitrypsin 78 1.312 1.302 0.967 1.941 1.288 1.256 0.845 e 84.68 63.40 103 0.895 0.888 0.790 1.060 0.619 1.319 0.741 m i
r 52.71 52.62 641737.1 HP Haptoglobin 41 0.578 0.980 1.120 3.523 1.417 1.040 1.258 e
p 47.98 51.43 39 1.439 1.739 1.187 0.564 0.576 0.746 1.008 x e
43.51 49.11 550991.3 SERPINA3, similar to ALPHA-1-ANTICHYMOTRYPSIN 33 1.264 1.393 0.761 2.296 1.691 1.227 0.789
Q 43.87 56.25 46 0.875 1.099 0.647 1.275 0.768 0.706 0.732 A
R 79.61 92.96 410714.5 HBA1;HBA2 Hemoglobin subunit alpha 161 0.849 0.906 1.057 0.842 13.371 1.461 10.099 T i 64.75 91.55 133 1.462 0.496 0.802 0.541 0.451 9.690 0.837 h t 92.49 93.88 654755.3 HBB Hemoglobin subunit beta 145 0.859 0.896 1.052 0.792 16.619 1.465 11.919 o b
57.45 93.88 87 1.469 0.708 1.058 0.724 0.609 7.495 0.842 n i
97.82 43.42 478003.2 A2M Alpha-2-macroglobulin 57 1.185 0.907 0.863 1.200 1.187 1.039 1.272 d
e 106.58 46.20 90 1.332 0.799 0.862 0.714 0.988 1.106 0.878 t
c 17.38 27.35 290315.4 CHGA Chromogranin-A 9 1.157 0.686 0.717 0.781 1.269 0.888 0.853 e t 26.67 44.86 20 0.642 0.986 0.631 0.691 1.130 0.495 0.836 e d 10.92 25.80 298828.3 APOH Beta-2-glycoprotein 1 5 0.878 0.561 0.945 1.277 0.815 0.933 0.982 s n
i 19.32 27.25 11 1.277 0.965 1.607 1.255 1.224 1.464 1.231 e
t 36.14 31.94 400826.1 CLU Isoform 2 of Clusterin 35 0.775 0.941 0.909 0.694 1.536 0.891 1.162 o
r 55.71 39.72 55 0.901 0.743 0.481 0.785 0.579 0.939 0.895 p 35.96 52.43 21841.1 APOA1 Apolipoprotein A-I 31 0.769 0.736 0.919 1.004 0.693 0.809 1.299 62.06 77.15 60 0.968 0.643 0.693 0.955 0.506 1.233 0.681 37.12 58.36 21842.1 APOE Apolipoprotein E 24 0.903 0.585 0.893 0.850 0.779 0.821 0.735 46.1 60.57 39 0.668 0.750 0.698 0.799 0.874 0.547 1.120 29.08 26.44 6601.5 CHGB Secretogranin-1 20 0.913 0.560 0.724 0.739 0.728 0.741 0.644 51.65 45.79 51 0.460 0.686 0.529 0.706 0.827 0.501 0.777 12.25 17.74 292071.6 SCG3 Secretogranin-3 6 0.964 0.745 0.794 0.833 0.932 0.932 0.728 32.68 44.23 17 0.772 0.914 0.732 0.850 0.917 0.723 1.039 30.15 37.35 426060.3 IGHA1 20 1.721 1.758 1.115 3.547 1.648 1.139 2.092
t 36.05 12.64 19591.2 cDNA FLJ55673, similar to Complement factor B 19 1.115 1.130 0.824 1.112 0.835 0.959 1.001 d n e e t 18.79 53.28 796379.2 B2M , highly similar to Beta-2-microglobulin 20 1.155 0.820 0.795 0.658 1.030 1.000 0.678 c m i e 45.91 65.91 304273.2 APOA4 Apolipoprotein A-IV 33 0.790 0.897 1.074 1.117 0.806 1.012 0.792 r t e e 16.11 30.33 218874.1 SPP1 Isoform B of Osteopontin 28 0.656 0.910 0.624 0.758 1.123 0.578 0.955 p d
x s 4.56 4.72 656113.2 SIRPA Signal-regulatory protein alpha 2 0.762 0.812 0.682 0.552 1.297 0.675 0.857 e n i e 4.5 3.55 24046.2 CDH13, highly similar to Cadherin-13 2 0.815 0.997 0.961 0.760 1.004 0.778 0.746 e n t o o 7.24 10.71 185662.4 CD99L2 3 0.748 1.010 0.940 0.758 0.955 0.711 0.825 r n p i 16.09 25.04 289501.2 VGF Neurosecretory protein VGF 10 0.593 0.778 0.785 0.759 0.785 0.623 0.796 SI Table 4 Full list of proteins identified in all three iTRAQ experiments, and both Sydney and Edinburgh studies. These are the full lists of proteins in three iTRAQ CSF experiments, not just those with significantly deregulated iTRAQ ratios; yellow = Sydney CSFs iTRAQ experiment 1, green = Sydney CSFs iTRAQ experiment 2, orange = Edinburgh CSFs iTRAQ experiment 3. The data represent 4-7 technical replicate runs, all searched on ProteinPilot v3.0. Only data with a ProteinPilot unused score of at least 1.3 (or greater) is presented, representing ≥95% confidence in the correct protein ID. The iTRAQ reporter ion ratios relative to the 119 control ion are shown, with significantly upregulated proteins highlighted in pink and significantly downregulated proteins highlighted in blue (p ≤ 0.05), the boxes with no colour being non-significantly different. The “low” and “high normal” headers represent the reporter ions used in the Edinburgh delirium study iTRAQ experiment (orange bars). The “mild delirium” and “moderate AD” headers represent the reporter ions used in each of the two Sydney delirium study iTRAQ experiments (yellow and green bars).
(A)This list represents all proteins identified in all three experiments (i.e., includes all identified proteins, not just the deregulated proteins). iTRAQ reporter ion ratios (all relative to 119 reporter = mild AD (no delirium) control) low normal high normal moderate delirium mild delirium mild delirium moderate AD
Unused %Cov(95) Accession Name Peptides(95%) 113:119 114:119 115:119 116:119 117:119 118:119 121:119 2.83 11.40 1 1.024 2.372 0.819 1.636 1.018 1.236 1.217 3.31 10.28 384399.1 Myosin-reactive immunoglobulin light chain 2 0.968 1.409 1.568 1.278 0.901 1.021 1.016 2 10.28 2 0.939 0.857 1.033 0.908 0.880 0.906 1.295 25.78 63.59 45 1.123 1.181 1.512 1.514 1.270 1.228 1.081 42.46 65.22 855916.1 Transthyretin 47 0.987 0.953 1.789 0.930 1.201 1.343 1.096 37.09 66.85 47 0.918 1.060 1.380 1.056 1.195 1.486 1.245 23.69 34.14 14 0.792 0.938 0.876 0.920 0.954 1.092 0.933 15.37 24.04 22895.7 A1BG Alpha-1B-glycoprotein 12 1.058 1.004 0.999 1.036 0.957 0.877 0.952 28.26 36.16 25 1.013 0.896 1.076 0.893 0.846 1.058 0.973 98.18 43.15 61 0.994 0.910 0.968 0.909 1.110 1.083 1.037 97.82 43.42 478003.2 A2M Alpha-2-macroglobulin 57 1.185 0.907 0.863 1.200 1.187 1.039 1.272 106.58 46.20 90 1.332 0.799 0.862 0.714 0.988 1.106 0.878 4.1 4.34 3 0.816 0.790 0.702 0.843 0.886 0.832 0.822 2.32 1.17 19943.1 AFM Afamin 1 0.651 0.967 1.132 0.934 0.584 0.878 0.891 5.24 3.34 2 1.053 0.782 0.927 0.747 0.837 0.986 0.884 40.97 37.11 25 1.181 0.799 0.874 1.302 1.189 1.058 1.184 24.53 27.84 32220.3 AGT Angiotensinogen 13 0.862 0.682 0.947 0.843 0.871 0.848 0.747 40.62 40.21 33 0.792 0.859 0.828 0.677 1.376 0.834 1.170 42.61 67.79 36 0.852 1.040 0.621 0.771 0.751 0.945 0.793 35.96 52.43 21841.1 APOA1 Apolipoprotein A-I 31 0.769 0.736 0.919 1.004 0.693 0.809 1.299 62.06 77.15 60 0.968 0.643 0.693 0.955 0.506 1.233 0.681 11.45 52.00 6 0.936 1.233 0.690 0.810 0.762 1.119 0.926 9.24 41.00 21854.1 APOA2 Apolipoprotein A-II 5 0.681 0.692 0.956 1.135 0.535 0.886 1.426 13.63 64.00 17 1.222 0.800 1.151 1.005 0.588 1.411 1.079 2.02 13.68 1 1.048 1.297 1.121 1.738 1.428 1.045 0.838 2 9.40 657670.1 APOC3 Apolipoprotein C-III variant 1 1 1.710 2.379 1.734 2.075 2 9.40 1 1.504 1.119 1.228 1.006 0.962 1.981 0.545 12.2 23.26 10 1.026 1.400 1.026 0.887 1.180 1.099 1.189 11.81 23.26 924574.1 APOD Putative uncharacterized protein APOD 8 0.940 1.451 0.939 0.965 0.866 1.006 0.790 11.34 21.40 8 1.517 1.482 2.056 1.374 2.486 1.508 1.826 40.29 58.36 23 0.848 0.722 1.156 1.172 1.390 0.992 1.141 37.12 58.36 21842.1 APOE Apolipoprotein E 24 0.903 0.585 0.893 0.850 0.779 0.821 0.735 46.1 60.57 39 0.668 0.750 0.698 0.799 0.874 0.547 1.120 14.75 25.80 7 1.345 1.323 0.955 1.033 1.341 1.290 1.299 10.92 25.80 298828.3 APOH Beta-2-glycoprotein 1 5 0.878 0.561 0.945 1.277 0.815 0.933 0.982 19.32 27.25 11 1.277 0.965 1.607 1.255 1.224 1.464 1.231 18.97 12.9913.82 23.76 9 1.0446 0.8470.991 0.9600.845 1.1310.969 1.2060.990 1.1460.867 1.1150.848 0.831 14.88 11.5645.9513.014 36.7023.057.056608.1 2147.4APP Isoform APP770 of AmyloidCHI3L1 beta Chitinase-3-like A4 protein (Fragment) protein 1 7 0.9663062 0.8491.0840.9100.900 0.8941.1211.3501.371 0.7760.9021.1251.351 0.7781.0340.9560.935 0.8211.0361.1581.156 0.8521.0991.0141.048 1.0181.1070.724 20.92 14.8134.0612.4410.11 24.6823.6314.62 26314.122417.4 LRG1 Leucine-richGSN Isoform alpha-2-glycoprotein 1 of Gelsolin 11 0.9931975 0.8791.0471.1970.709 0.9411.1281.0390.803 0.7760.9371.1180.680 1.0630.8501.5340.657 0.7440.8771.5230.802 0.9640.9441.1710.818 0.7660.8700.854 3.71 4.8949.819.497.39 39.6421.6116.34 2 1.4893554 0.8481.0681.044 0.9191.0671.1310.776 1.5000.7511.1420.865 1.4471.0530.9220.955 1.6011.0930.9700.894 0.7581.4820.997 0.9510.9011.112 1.72 1.9221.219.214.06 58.4516.8611.88784119.1 9028.1 ATP6AP1 V-type proton ATPaseCLEC3B subunit Tetranectin S1 1 0.6744742 0.5590.9450.9660.874 0.7530.4600.8680.928 0.7781.1840.9680.862 0.6920.6141.1620.620 0.7390.3591.4571.409 0.8991.2370.964 0.8161.3850.976 6 9.1579.617.83 92.9616.34 410714.5 HBA1;HBA2 Hemoglobin subunit alpha 3 0.7511614 0.7320.8490.713 0.7810.9060.860 0.8241.0570.802 0.8530.8420.746 0.71813.3711.007 0.5031.4610.761 10.0991.052 8.06 16.86 13303.2 LSAMP Limbic system-associated membrane protein iTRAQ reporter4 ion ratios1.093 (all relative0.894 to 119 reporter0.925 = mild AD0.928 (no delirium)1.058 control) 0.962 0.969 11.67 25.5064.75 91.55 7 0.859133 1.0971.462 1.0440.496 1.2570.802 1.1260.541 1.0710.451 0.9789.690 0.837 15.036.79 10.9511.64 38 0.7291.083 0.8710.823 0.8050.860 0.6831.119 low normal1.1121.085 high normal0.7120.982 0.8910.825 12.08 23.4935.14 93.88 5 0.91342 1.1201.011 0.9360.356 1.1071.119 0.8230.427 1.0130.346 0.7821.065 0.731 13.027.26 166729.48.587.72 7257.4 AZGP1 Zinc-alpha-2-glycoproteinCLSTN1 Isoform 2 of Calsyntenin-1 (Fragment) moderate37 delirium0.9230.992 0.9070.829 mild0.8370.808 delirium 1.0050.869 mild delirium0.8111.094 moderate0.9620.958 AD 0.9900.779 Unused22.06 %Cov(95)38.2692.4917.075.245 Accession93.8810.9012.676.21 654755.320986.2 Name HBB HemoglobinLUM Lumican subunitPeptides(95%) beta 12113:119 1.1541451024 114:119 1.2680.8591.0751.3960.823 115:1191.4540.8961.0691.1240.857 116:1191.1211.0520.8521.2110.955 117:1191.4340.7920.6471.6200.762 118:1191.25416.6190.8702.4911.038 121:1191.2021.4651.0331.3540.869 11.9191.1361.3761.132 28.9315.6 45.8821.4557.4515.5338.432.98 2714.293.8830.4734.136.16 470716.1DKK3, similar to Dickkopf-relatedSCG5 Isoform protein 2 of Neuroendocrine 3 protein21 7B2 9 0.939 1.094873482 0.643 0.7951.4691.0151.0390.886 1.0831.0810.7081.1230.9590.792 0.9331.0451.0581.0381.0010.880 1.2021.5520.7241.0940.9801.055 1.0431.0950.6091.1581.2380.838 1.2241.1327.4951.2031.0770.945 0.8421.1751.0110.912 11.344.51 20.052.6520.0136.1423.76 46.9413.8710.9031.949997.1 400826.1B3GNT1 beta-1,3-N-acetylglucosaminyltransferaseCLU Isoform 2 of Clusterin7 1 1.118 0.831203593 0.850 0.5361.0281.0930.8130.775 0.8200.6230.7760.8220.9520.941 0.8350.5181.0901.1220.7740.909 1.0810.7660.5110.9870.7410.694 0.9520.9050.6061.2251.2171.536 0.7800.7140.6571.0471.0930.891 0.6301.0921.1621.145 7.544.25 10.887.9510.2383.0555.7113.1 18236.285.0361.4839.728.74 473011.3795918.1GM2A GangliosideNCAM1 GM2 IsoformHBD activator Hemoglobin 1 of Neural subunitcell adhesion delta2 molecule3 10.954 0.7138876556 0.856 0.8630.9440.8990.8630.901 0.9460.6440.9550.7921.3680.743 0.9680.6481.1900.9231.4660.481 1.0901.0600.9290.7190.7960.785 1.2940.5457.2301.1271.0300.579 0.9590.9831.0200.9421.0900.939 4.4280.7470.9160.895 5.14.5 10.881.878.0425.1587.0626.87 76.1916.9068.4232.15 553177.1 SERPINA1 Isoform 1 of Alpha-1-antitrypsin2 1 1.139 0.91252127816 0.859 0.8121.6390.8221.3121.271 1.0531.0120.5340.8931.3020.771 0.9050.9231.1710.9470.9671.016 1.0271.1950.6020.7871.9410.974 1.0901.0990.6571.1841.2881.023 0.9381.1158.1060.7211.2561.215 0.5451.0001.0840.845 2.126.18 24.11.2138.8884.6813.498.68 21855.151.1921.3963.4016.57456623.2 64667.4 APOC1BCAN ApolipoproteinIsoform 1 of CNDP1Brevican C-I Beta-Ala-His core protein dipeptidase3 1 1.015 1.0583010337 0.896 0.8721.3111.0490.8950.871 0.9550.9502.1850.9360.8880.711 1.2530.8970.7821.0040.7900.934 0.8580.7660.9170.9101.0600.704 0.8910.8931.1431.0580.6191.296 1.2431.0440.9171.0361.3191.033 1.0750.9900.8270.741 3.52 24.1 2 1.123 0.686 0.615 0.866 0.715 0.941 0.875 3.7 1.9852.7137.4232.024.47 52.6245.7646.359.45 641737.1301579.4 NPC2, highly similarHP to Haptoglobin Epididymal secretory protein2 E1 0.9264129222 0.9390.5780.9740.8660.575 0.9770.9800.9751.4950.812 0.8881.1201.0611.5481.731 1.0753.5230.8051.0220.565 0.8811.4170.9251.1421.065 1.0101.0401.0291.1350.708 1.2580.8471.0160.957 2 4.082 22392.1 C1QA Complement C1q subcomponent subunit A 1 1.097 1.827 0.997 1.068 1.179 1.049 0.655 179.93 61.1547.9843.5139.027.91 51.4325.3749.1121.88 550991.3 SERPINA3, highly similar to ALPHA-1-ANTICHYMOTRYPSIN104 0.9963933214 1.0941.4390.8211.2640.999 0.9911.7390.8891.3931.062 1.0091.1870.7770.7611.070 1.1580.5640.8092.2961.111 1.1710.5760.9901.6911.139 1.1820.7460.9691.2271.268 1.0081.0501.0710.789 2.61 5.306 1 1.016 1.164 1.140 1.008 1.152 1.052 1.273 157.69 52.5637.9413.2843.8748.91 46.7556.2527.61783987.25.35 17601.1 C3 Complement C3 (Fragment)CP Ceruloplasmin 89 1.0503146296 0.8850.9191.0480.8751.320 0.9490.9230.8151.0991.090 1.0851.1031.0720.6471.033 1.1730.9941.0271.2751.203 1.0701.0411.3550.7681.054 1.0201.1031.1540.7061.023 0.8880.9590.8810.732 7.21 19.4 22420.3 RBP4 Retinol-binding protein 4 4 0.878 1.342 1.163 0.904 0.795 0.988 0.800 157.97 52.1942.6257.316.73 51.0811.1133.15 22488.1 HPX Hemopexin 129 1.18031424 1.0770.8000.8960.987 1.1610.9960.9680.837 0.9811.1630.9220.902 1.0361.0951.1330.998 1.1321.1881.0590.824 1.0571.0441.0091.189 0.9870.7720.848 8.17 22.397.79 2.91 873446.2 NRCAM Isoform 5 of Neuronal cell adhesion5 molecule0.996 3 1.153 1.043 1.176 0.821 1.1340.772 1.0460.719 1.0650.866 0.7620.865 0.677 6.1 3.9142.740.31.7 49.3564.384.20 3 1.32249522 1.0201.0230.9710.999 0.9481.0020.9710.632 0.9741.1941.2001.227 1.0681.1250.8650.993 1.0490.9920.5321.254 0.9371.1511.0141.054 0.9831.1480.906 8.32 16.1915.53 22426.17.03 27482.1 AMBP ProteinSERPINA6 AMBP Corticosteroid-binding globulin6 0.867 8 1.343 0.813 1.005 0.870 0.9170.870 0.7720.708 1.0601.193 0.8840.607 0.919 15.35 9.7318.42 22.10296608.6 C7 Complement component C7 7 1.2579 1.3360.919 0.9300.864 1.1100.710 1.1940.927 1.0950.784 0.8630.962 0.737 4.9 7.10217.898.263.7 10.9648.636.42 32293.1 CST3 Cystatin-C 2 1.164 3532 1.020 1.0120.8950.934 1.387 0.8450.8140.698 1.0510.8901.0700.871 1.3910.9390.9850.731 1.1880.9330.7841.033 1.2871.0340.7781.027 0.9300.6430.903 10.04 5.9314.63 18.29 22371.1 HRG Histidine-rich glycoprotein 5 0.9047 0.9530.706 1.0390.863 0.7831.232 1.0820.941 0.7890.862 0.8210.925 1.036 14.72 14.0927.4536.137.41 22431.210.6731.4773.29 25465.2AHSG, similar to Alpha-2-HS-glycoproteinOGN cDNA FLJ59205, highly similar to7 Mimecan 1.055 16512 0.863 0.7920.9290.694 1.087 0.9671.0440.808 0.6100.9540.9070.817 0.5780.8081.0920.915 0.7090.9321.2081.199 1.0890.9710.9840.739 0.7620.9040.948 7.1817.5 25.46.6215.1910.8222.146.15 18.6718.2622.635.36 32179.3 SERPINC1 Antithrombin-III18 3 0.934 1.07571473 0.851 1.2681.2080.8960.8941.137 1.1801.1690.9360.9181.0040.989 0.9711.0660.9370.8981.1981.034 0.7251.1731.0010.8701.2010.911 0.9831.0670.8010.9280.9021.086 0.9591.0921.4111.0781.0111.052 0.9280.8880.9550.809 13.726.03 79.1112.7010.0231.9833.013.71 22434.427.0849.7535.782.4622395.1 28911.2ALB Putative uncharacterizedC9 Complement protein componentDAG1 ALB Dystroglycan C9 752 6 1.585 0.996747202 0.810 1.1291.0411.0130.9861.027 0.7910.9701.1052.2680.9231.116 0.7721.3211.1241.9961.0751.231 0.5641.1521.1361.2451.0560.930 0.8631.0821.0551.3120.8421.072 0.7560.9271.0561.2610.9591.119 0.9951.1791.2330.935 14.935.72 84.5315.746.1236.3410.256.86 17.9240.307.785.59 29235.1884926.1 IGFBP6ORM1 Insulin-like alpha-1-acid growth glycoprotein factor-binding 1716 precursor protein 67 1.010 1.2453415 1.549 1.2170.9711.5140.8880.793 1.0011.0641.1491.4351.0890.957 1.4091.4051.0871.2310.8590.918 0.9981.0900.8902.5701.0630.783 0.9561.1360.9091.9881.0331.054 1.2020.9010.9991.2461.0300.950 0.8200.7270.9010.707 3.74.1 3.5538.0538.5120.2869.54 24046.215.8351.7410.2512.73 CDH13292950.4 cDNA FLJ52398, highly similarSERPIND1 to Cadherin-13 Serpin peptidase inhibitor2 2 1.070 0.981549104 0.746 0.3450.8841.2140.9280.892 1.0731.5801.0441.2991.0220.894 1.0520.2080.9941.5441.0870.990 1.1670.2480.9771.6661.1051.302 1.0940.6581.1681.2101.0991.187 0.8781.1971.0441.5480.8871.140 0.9971.1161.0121.072 17.134.5 3.55341.006.0412.8310.6712.47 15.2548.7610.63215983.39.01 878576.5 CA1ENPP2 Carbonic Isoform anhydrase 3 of Ectonucleotide 1 pyrophosphatase2 160.815 1.04331976 0.997 0.9601.0511.0281.0450.968 0.9611.1350.8161.2000.9620.940 0.7600.9671.4081.2341.2531.370 1.0043.0181.1001.3960.9770.819 0.7781.0431.4470.8100.9220.993 0.7462.8351.4201.1030.8511.113 1.5430.8540.8910.850 10.018.01 18.6919.162.0113.4937.2221.07 27350.34.6134.3345.6913.06 16915.120091.1 PRDX2 Peroxiredoxin-2IGFBP7 Insulin-likeORM2 Alpha-1-acid growth factor-binding glycoprotein3 protein 2 76 1.070 2.3291112214 1.084 1.0580.7131.1141.0380.947 1.1801.5190.7211.1791.0150.885 0.9680.7521.2531.0881.0910.934 5.6320.9930.6861.4561.1960.952 1.2214.4111.2571.3481.3110.927 4.2480.8751.4121.1701.2831.400 1.2390.7931.1400.764 11.724.47 13.6423.477.4112.5230.9418.92 15.2544.7839.7123.15 6114.4 SERPINF1 Pigment epithelium-derived2 factor 6 1.350 0.9633151610 0.798 0.7860.7661.0690.9471.019 0.9330.7510.9530.9310.9771.302 0.8241.1470.8241.2721.2881.031 0.8740.9860.8060.9850.8431.055 4.0721.0251.0400.7971.0071.014 0.8631.0671.3431.5211.1441.088 1.1390.9300.9750.805 6.04 6.818 31121.2 CPE Carboxypeptidase E precursor 3 0.944 0.840 0.955 1.135 0.993 0.902 0.864 5.66 9.6062.2836.185.377.01 53.1847.854.906.9129260.2 19568.1 CD14 Monocyte differentiationF2 Prothrombin antigen (Fragment)CD14 3 1.212812423 1.0660.8761.2270.8280.942 0.9691.4921.0100.9131.060 1.0821.0760.8140.9971.205 1.8280.9761.0730.8291.252 1.1630.7720.8311.0781.050 0.9231.1650.9701.2970.899 1.0570.8510.8621.025 11.07 12.59 5 0.819 0.763 0.766 0.606 0.873 0.781 0.811 13.3 22.1352.4930.6210.312 52.3334.0010.932.45 876888.1299738.1 IGHG1;LOC100294459;LOC100290146;IGHV4-31PCOLCE Procollagen C-endopeptidase enhancer cDNA FLJ78387 17 0.889741818 0.9520.9491.4411.0721.198 0.9171.0021.1991.1081.156 0.8150.6961.1090.9651.341 1.1201.7071.3941.0841.124 0.8531.1491.7311.2311.056 1.0301.3241.2851.1741.060 0.9451.5041.1030.987 2 2.268 44369.2 PLXDC2 Isoform 1 of Plexin domain-containing protein 2 1 1.159 0.798 1.264 0.866 1.217 0.990 0.528 3.4 9.3847.1620.682.547.5 44.0722.6018.942.45 291866.5 SERPING1 Plasma protease C1 inhibitor 2 0.921791113 0.9151.2330.9671.0041.003 0.9641.0501.0881.1290.707 0.9023.3181.2521.0420.889 1.0321.0531.0181.2460.995 1.0042.0971.3140.9771.122 1.0011.7770.9901.0321.031 1.1891.1651.1990.680 2.38 2.268 1 0.904 1.241 0.755 1.472 0.952 1.465 1.170 2 9.385.7110.9628.356.91 27.5230.3829.0014.9811302.1 334282.2 CD59 CD59 glycoproteinFAM3C Protein FAM3C 1 0.869352853 1.8871.0400.6361.0211.131 0.6671.2520.6841.0780.821 2.8050.8011.1051.0480.909 2.0600.9231.3400.9720.895 0.7301.2121.1931.1440.996 1.0531.0141.1661.0051.059 0.9471.6520.8601.084 2.02 1.108 165125.6 C14orf37 cDNA FLJ59350 1 1.056 0.690 1.093 1.021 1.183 1.132 1.131 2.51 9.383.713.7311.02 28.9971.4326.43 930442.1 IGHG4 Putative uncharacterized protein DKFZp686M242181 1.0573985 1.1000.8160.8170.755 1.2051.4410.5690.897 0.9370.7930.8600.973 1.3132.8171.2810.828 0.9451.3940.9911.104 1.1121.4030.8770.691 0.8971.0490.903 2.01 1.1082.05 3.85 2280.1 PCSK1N ProSAAS 1 0.757 1 0.872 1.059 0.769 0.702 0.7090.624 1.0480.806 0.5801.021 1.0280.858 0.649 2.3 1.322.11 17.86 1 1.08530 0.8211.406 1.0071.120 0.8201.175 1.1541.197 0.9671.347 0.8291.101 0.799 4.35 6.49711.038.7112.8 176221.720.0053.9010.82 218733.6NEGR1 Neuronal growthSOD1 regulator Superoxide 1 dismutase [Cu-Zn]2 0.988 57 0.846 0.8961.0490.916 0.984 0.9550.7711.545 1.2011.1940.8700.955 1.3990.8900.9150.884 1.1950.8661.0961.020 1.1690.9551.0251.038 0.9641.2040.934 2.09 0.00 290085.2 CDH2 Cadherin-2 0 1.176 0.599 0.632 0.715 1.028 0.930 0.657 2.56 3.6726.9412.271.566.3 9.0931.176.178.46 889740.1 FBLN1 Fibulin 1 1 0.825 3456 0.929 1.5730.8270.7281.131 0.741 1.2310.9490.9401.298 0.7561.8230.9180.9371.583 1.1052.0810.9290.6230.822 0.9360.7810.9821.1671.143 0.9031.1290.9630.7461.177 0.8200.9320.8701.121 4.02 2.76 2 0.865 0.987 0.801 0.934 0.883 0.706 0.845 16.82 10.2312.9116.274.497.7 216641.115.8622.5014.704.32 946337.119580.1CNTN1 Isoform 2 of Contactin-1IGHMPLG 52 Plasminogen kDa protein 8 1.031 61224 0.834 1.4590.9150.9411.041 1.146 1.1420.8560.9191.231 1.1170.8400.9691.1571.426 1.2372.2951.0421.0200.928 1.1481.1840.8651.1431.343 1.0291.0090.9621.2881.099 2.1651.0241.1301.003 23.192.34 15.895.776.0915.796.596 6.5519.1710.975.18 27827.2 SOD3 Extracellular superoxide dismutase12 [Cu-Zn]1 0.875 0.905238 0.897 0.9832.1251.1270.9521.014 0.8971.3251.0081.0351.0481.439 0.7531.0240.9081.0901.0401.233 1.2701.0081.7411.0460.8811.209 0.7370.9901.0861.1270.7921.119 1.0341.0551.3011.0460.9641.161 0.9611.0601.1830.863 12.451.9 5.583.859.132.846.618 218192.340.5420.0019.98165972.37.21 ITIH4 Isoform21885.1 2 of Inter-alpha-trypsinCFD ComplementFGA factorinhibitor Isoform D preproprotein 1heavy of Fibrinogen chain H4 alpha5 chain 1 1.095 1.055372245 1.042 1.4431.0080.9770.9821.513 1.0711.6071.2510.8591.0531.138 1.5411.0110.9731.0301.1820.971 1.5061.2841.1041.0270.8651.819 1.0301.0761.1650.6721.2132.827 1.0201.5311.1500.9571.1130.953 1.0520.9820.8541.118 21.862.05 12.479.237.1541.8822.594.21 34.7534.3417.095.85 418153.1643034.3 IGHMPLTP, Putativehighly similar uncharacterized to PHOSPHOLIPID protein TRANSFER DKFZp686I1521211 PROTEIN1 1.307 0.8024227153 1.050 1.1180.9170.8850.7191.088 1.0811.2301.3111.1140.6281.195 1.3150.9700.8670.9201.0831.005 1.0310.9782.1690.9791.0151.326 1.0420.9711.2041.1301.3750.834 1.0380.6901.2161.1291.2860.937 1.1701.0451.1580.869 29.332 1.84213.575.2524.168.179.9 218413.228.7611.1120.3315.48 296777.4 BTD Biotinidase SPARCL1 SPARC-like protein1 1 130.940 1.043481545 0.842 1.0201.1291.0091.0341.047 0.7440.9730.9400.9540.6501.261 1.0130.9791.4231.1760.7991.039 0.8331.0441.1300.8390.7791.012 1.0001.0420.9821.1220.8211.044 1.2551.0391.4610.9690.9111.121 1.1921.0241.0680.655 17.722.51 1.8428.2942.1735.96416.8 23.8468.4231.1722.4029739.5 298497.3 CFH Isoform 1 of ComplementFGB Fibrinogen factor beta H chain1 9 1.043 1.0564743710 0.977 1.0210.9641.2610.6511.862 1.1551.0221.2310.8700.7801.025 0.7371.0221.1301.3580.7880.892 1.0671.0070.8891.0430.7692.088 0.8990.9910.9931.7140.8431.306 1.1900.9361.1311.1790.5980.934 1.0301.3871.0770.889 19.628 22.317.644.28118.5330.1912.68 218414.516.2849.4772.4916.50 782983.213179.1 CA2 CarbonicIGHV3-7 anhydrasePTGDS hypothetical Prostaglandin-H22 protein D-isomeraseXP_0023475225 110.940 1.0531792368 0.964 1.0301.0370.8581.0421.119 1.0651.0951.1670.8430.9151.211 0.8720.9001.0451.0000.9681.116 4.3191.0841.5050.6130.9931.207 1.1250.9940.9851.0101.4380.783 4.0231.0211.1691.0941.2771.055 1.0160.6391.2360.958 24.545.75 11.9243.33121.093.743.147.12 16.2868.9573.218.46 22463.1 TF Serotransferrin 3 151.374 1.0071283705 0.716 0.7031.1460.7551.0080.847 1.1200.9721.0351.0260.9961.461 0.7031.0341.6821.2331.1870.842 0.8451.4130.8630.7530.7371.520 4.0711.2451.2711.5970.8681.201 0.8551.3071.3260.5050.9671.110 1.1031.1901.2220.941 2.04 6.952 219446.5 PEBP1 Phosphatidylethanolamine-binding protein 1 1 0.988 1.066 1.110 1.123 1.637 1.245 1.569 17.38 27.3518.47109.6121.135.36 52.3430.1365.7625.84290315.4 877792.1 CHGAFGG Chromogranin-A Putative uncharacterized protein FGG 9 1.15727127122 0.6861.0660.8121.2091.725 0.7171.6620.6251.6591.213 0.7810.8811.1231.6140.894 1.2690.8521.2641.2931.865 0.8880.9371.2591.4521.069 0.8531.1181.2091.0000.924 1.0021.2201.0491.041 4 14.97 2 0.792 0.956 0.902 0.775 1.099 0.957 1.359 26.67 44.8621.4712.974.967.43 50.6430.1320.677.11 784985.114048.1 RNASE1IGK@ Ribonuclease IGK@ protein pancreatic 20 0.64230359 0.9861.3280.9711.0440.976 0.6311.4750.8131.1621.208 0.6910.8491.0471.1040.926 1.1302.0530.9630.8501.472 0.4951.0821.2111.1680.734 0.8361.3051.2901.1690.613 1.1820.6491.0590.948 4.19 4.398 220562.3 NPTX1 Neuronal pentraxin-1 2 1.006 0.814 1.194 1.536 1.334 1.444 1.177 36.33 32.9412.6632.346.854.86 42.9830.133.978.38 298971.1 VTN Vitronectin 25 1.167201542 0.8001.3660.9110.9990.992 1.0930.9401.2710.8120.962 1.0871.3891.5321.1140.991 1.2351.1210.8501.3200.994 1.0981.2291.9490.9171.009 1.3431.0660.7701.0001.055 0.7541.2031.1531.029 1.51 1.852 1 0.740 0.909 0.849 0.673 1.235 0.725 1.065 29.08 26.4418.6911.4425.443.9 48.3614.643.576.576601.5 845263.1 CHGBFN1 Secretogranin-1 fibronectin isoform 2 preproprotein 20 0.913151227 0.5601.1410.8691.2900.928 0.7240.6440.6681.3640.729 0.7391.0421.0471.3460.893 0.7280.9840.9811.3360.618 0.7411.3351.1261.0391.047 0.6441.1121.1161.2520.942 1.2071.2411.0771.021 18.73 20.49 289501.2 VGF Neurosecretory protein VGF 9 0.673 0.710 1.092 1.145 1.105 1.325 1.493 51.65 45.7949.67 13.51 51 0.46030 0.6860.778 0.5291.455 0.7060.925 0.8270.849 0.5010.988 0.7770.863 0.968 16.09 25.0416.974.08 43.033.89 23845.19362.2 KLK6 SCG2Isoform Secretogranin-2 1 of Kallikrein-610 0.593 92 0.778 0.7991.256 0.785 0.6411.110 0.7590.9810.886 0.7850.5761.652 0.6230.8840.844 0.7960.9771.249 0.6681.044 1.55 1.36216.5539.217.74 291136.445.4946.865.35 COL6A1 Collagen alpha-1(VI) chain 1 1.049 9255 1.118 0.9270.6340.944 1.253 0.9700.8101.121 1.0401.1150.7380.943 1.2060.7010.6060.939 1.1991.6280.8531.061 0.9760.9020.6571.029 1.1860.8470.872 5.29 2.62617.8918.9330.11 18.9719.6629.82 968027.1 GC;C16orf13 Putative uncharacterized protein2 C16orf130.925 81018 0.920 0.8521.1260.910 1.006 1.0680.8180.939 0.7640.8441.4341.045 0.9331.1021.0391.250 1.3410.9561.4870.928 0.8550.9671.2840.899 0.8691.3700.852 3.13 5.78314.2312.2530.22 292946.116.8617.7432.45 215894.1292071.6SERPINA7 Thyroxine-bindingKNG1 globulinIsoformSCG3 Secretogranin-3 LMW of Kininogen-13 1.181 7256 0.765 1.0470.9641.043 1.052 1.0240.7450.922 1.2201.1990.7941.008 1.0031.3190.8330.923 0.9000.9720.9320.827 1.1380.9030.932 1.1340.7280.935 4.53 4.81917.4232.68 18.7444.23 2 0.873 1017 0.821 1.1090.772 0.956 1.0810.914 0.7961.1710.732 0.7291.1130.850 0.8191.1620.917 0.9420.9780.723 1.9021.039 2.17 1.627 294004.1 PROS1 Vitamin K-dependent protein S 1 0.820 1.134 0.944 1.054 0.916 1.038 1.119 6.06 5.03 3 0.986 0.915 1.173 0.794 0.907 2.381 0.913 2.01 2.273 295832.1 OMG Oligodendrocyte-myelin glycoprotein 1 0.852 0.685 0.986 1.198 1.191 1.323 1.193 2.01 2.273 1 0.865 0.962 1.158 0.974 1.374 0.985 1.052 3.24 1.252 296165.6 C1R, highly similar to Complement C1r subcomponent 1 1.481 1.258 0.831 1.379 1.003 1.540 1.680 5.84 4.868 2 0.971 1.135 0.918 0.930 1.044 1.016 0.839 12.1 10.38 296534.2 FBLN1 Isoform D of Fibulin-1 7 0.991 0.962 1.162 0.884 1.165 1.018 1.042 2.52 9.246 7 0.922 0.997 0.759 1.022 0.806 1.013 0.906 5.47 9.756 297284.1 IGFBP2 insulin-like growth factor-binding protein 3 1.108 1.051 0.927 0.815 1.002 0.976 1.092 5.04 3.049 2 0.862 0.972 0.981 0.663 0.679 0.828 1.023 24.26 14.62 299059.6 CHL1 Neural cell adhesion molecule L1-like protein 14 0.871 0.788 1.030 0.946 1.233 0.964 1.024 8.14 5.065 4 1.071 0.717 0.722 0.624 1.047 0.760 0.731 29.47 39.39 304273.2 APOA4 Apolipoprotein A-IV 16 0.824 0.869 0.661 1.136 0.714 0.848 0.730 45.91 65.91 33 0.790 0.897 1.074 1.117 0.806 1.012 0.792 2.12 2.08 395488.2 VASN Vasorin 1 0.905 0.890 1.010 0.942 0.925 0.963 0.891 1.71 1.783 1 0.868 1.083 1.366 0.819 1.186 1.222 0.679 23.63 52.76 399007.7 IGHG2 uncharacterized protein DKFZp686I04196 51 0.824 1.203 1.075 1.802 1.105 1.399 1.078 16.65 35.01 57 1.311 0.701 0.790 1.318 0.792 1.845 0.917 103.3 34.17 418163.3 C4B complement component 4B preproprotein 58 0.956 0.959 0.984 1.033 1.241 1.216 1.072 83.1 27.35 43 0.812 0.928 1.059 0.996 1.212 0.927 0.828 24.48 28.66 426060.3 IGHA1 uncharacterized protein DKFZp686J11235 14 1.073 1.021 0.601 0.893 1.043 1.159 1.170 30.15 37.35 20 1.721 1.758 1.115 3.547 1.648 1.139 2.092 1.52 5.199 446290.1 LOC100131068 cDNA FLJ42349 fis 1 1.184 1.303 1.445 1.281 0.788 0.889 0.889 1.82 5.199 1 0.839 0.821 1.082 1.062 0.708 1.169 0.621 4.7 5.426 451625.1 CRTAC1 Isoform 2 of Cartilage acidic protein 1 2 1.024 0.924 1.206 1.078 1.464 1.129 0.846 6.01 6.977 3 1.137 1.047 1.376 1.048 1.062 0.969 0.875 2 10.91 455584.4 - Putative protein FAM86C-like 1 1 0.925 1.010 2.117 0.863 1.562 0.811 1.244 1.4 10.91 1 0.814 1.018 0.966 0.763 1.695 0.347 1.353 2.01 16.39 552578.2 SAA2;SAA1 Serum amyloid A protein 1 0.537 1.014 1.135 1.488 0.754 0.881 0.848 4.57 27.87 2 1.591 1.158 0.827 1.547 2.088 1.396 0.788 6.82 26.9 555577.1 THY1 Thy-1 cell surface antigen variant (Fragment) 5 0.935 0.950 1.116 1.031 1.459 1.242 0.934 4 17.24 2 0.972 0.800 0.950 0.977 1.375 0.985 0.978 27.16 25.5 607600.1 APLP1 Isoform 2 of Amyloid-like protein 1 17 0.765 0.782 1.027 1.097 1.336 1.125 1.204 18.36 18.43 11 0.950 0.813 0.925 0.810 0.935 0.948 0.822 1.7 41.51 642632.2 IGLC7 Ig lambda-7 chain C region 8 1.912 1.199 0.967 1.862 1.060 1.786 1.182 2 50.94 10 0.786 0.678 1.049 1.311 0.562 1.446 0.861 3.82 2.639 749179.2 C1S Putative uncharacterized protein C1S 2 0.857 0.915 0.790 0.930 0.884 0.873 0.743 6.15 6.891 4 0.937 1.006 0.773 0.813 1.052 0.963 0.966 20.17 56.56 796379.2 B2M similar to Beta-2-microglobulin 27 1.337 0.906 0.941 1.232 1.402 1.273 1.274 18.79 53.28 20 1.155 0.820 0.795 0.658 1.030 1.000 0.678 9.14 9.116 797539.1 NELL2similar to Protein kinase C-binding protein NELL2 5 0.827 0.715 0.897 0.981 1.045 0.949 0.894 4.17 4.144 2 0.883 0.909 0.827 0.645 1.042 0.829 0.817 1.72 37.02 827875.1 IGLV1-51 Lambda-chain 20 1.043 1.050 0.483 0.958 0.504 0.557 0.626 4.02 37.02 21 1.189 1.409 0.982 2.545 1.203 1.327 1.367 3.08 25.75 829640.1 IGLV3-19 IGL@ protein 18 0.774 0.917 0.487 0.664 0.670 0.855 1.348 6.57 33.91 28 1.071 0.841 0.937 1.369 0.986 1.020 1.008 2.26 0.905 855821.1 NRXN1 neurexin 1 isoform alpha2 precursor 1 1.254 1.039 0.893 1.034 0.991 0.944 0.440 3.87 0.905 1 0.976 1.184 0.831 0.873 0.771 1.258 0.917 1.52 3.846 873113.1 CAPZA2 Putative uncharacterized protein CAPZA2 1 0.804 0.608 0.844 0.888 0.790 0.848 0.908 1.7 3.846 1 1.104 0.695 0.807 0.612 0.618 0.936 0.817 8.15 5.323 873201.1 PSAP Isoform Sap-mu-6 of Proactivator polypeptide 4 1.118 0.740 1.065 1.028 1.382 1.140 1.160 3.24 1.711 1 0.965 0.704 0.857 0.587 0.816 0.981 0.774 6.05 13.56 879625.1 VSTM2A V-set and transmembrane domain-containing 3 1.080 0.700 1.011 0.854 1.679 1.236 1.368 2.03 5.508 1 1.154 0.535 0.505 0.514 0.943 0.675 0.482 4.02 27.73 916434.1 Anti-(ED-B) scFV (Fragment) 5 0.757 1.019 0.762 0.674 0.884 1.106 0.980 4.93 22.27 4 0.949 0.952 1.288 0.972 1.212 0.850 0.922 - cDNA FLJ52702,3.45 highly3.647 similar to918020.1 Homo sapiens CD44 antigen (homing function and Indian blood group system)1 (CD44), transcript0.759 variant0.650 4, mRNA 0.946 1.014 0.813 0.795 0.879 3.16 3.647 2 0.854 0.835 0.831 0.696 0.998 0.715 0.907 25.92 6.793 939824.1 141 kDa protein 11 0.869 1.190 1.060 0.890 1.182 1.157 1.147 25.06 7.741 10 1.104 1.017 1.045 1.170 1.188 1.218 1.033 6.28 15.27 943257.1 CD99L2 Isoform 1 of CD99 antigen-like protein 2 3 1.036 0.688 0.965 0.859 1.015 1.032 0.795 3.7 10.69 2 1.110 0.779 0.903 0.866 0.963 1.214 0.733 5.75 11.79 956325.1 PRNP Isoform 2 of Major prion protein 3 1.212 0.756 0.920 0.669 1.060 1.079 0.743 6.06 9.35 5 0.791 1.112 0.997 0.805 1.131 0.919 1.051 4 3.993 966295.1 CFI Light chain of factor I 2 1.291 1.129 1.244 1.012 0.969 1.213 1.384 4.69 3.993 2 0.944 0.953 0.994 1.062 0.912 0.933 1.017
(C)This list represents all proteins identified in only one experiment (i.e., includes all identified proteins, not just the deregulated proteins). iTRAQ reporter ion ratios (all relative to 119 reporter = mild AD (no delirium) control) low normal high normal moderate delirium mild delirium mild delirium moderate AD Unused %Cov(95) Accession Name Peptides(95%) 113:119 114:119 115:119 116:119 117:119 118:119 121:119 4 29.06 3111.7 IGKV1-33; Ig kappa chain V-I region AU 2 0.898 0.862 0.742 0.608 0.771 0.908 0.768 6.73 15.46 15614.4 PRSS3 Isoform A of Trypsin-3 3 0.778 1.753 1.748 2.178 3.114 1.921 2.164 9.6 8.29 17696.1 C1S Complement C1s subcomponent 4 1.267 1.021 0.863 0.927 1.005 1.164 1.123 2.38 0.34 24284.5 HSPG2 heparan sulfate proteoglycan core protein 1 1.076 1.066 1.023 1.047 1.007 1.230 0.995 1.71 2.60 29723.1 FSTL1;MIR198 Follistatin-related protein 1 1 0.784 0.684 0.857 0.617 0.776 0.767 2.01 3.38 31821.1 ITM2B Integral membrane protein 2B 1 2.052 2.055 2.692 1.213 2.136 1.311 1.703 2.16 5.80 32292.1 TIMP1 Metalloproteinase inhibitor 1 1 1.303 0.935 1.069 1.171 0.936 0.909 0.943 1.52 3.79 63334.3 TMEM41A Transmembrane protein 41A 1 0.625 0.767 0.976 1.039 0.736 0.895 0.967 2.03 2.78 152143.4 ZNF519 Zinc finger protein 519 1 0.746 1.043 1.074 1.279 1.706 1.460 1.689 20.46 44.02 154742.6 IGLV2-14;IGLC2 IGL@ protein 21 1.148 1.671 1.083 1.351 1.199 1.195 1.564 2.01 1.21 159927.2 NCAN Neurocan core protein 1 0.682 0.698 0.749 1.136 0.764 0.789 0.930 2.01 2.60 163207.1 PGLYRP2 N-acetylmuramoyl-L-alanine amidase 1 1.100 1.110 1.271 1.089 1.127 1.003 0.458 6.03 18.94 163563.3 PEBP4 Phosphatidylethanolamine-binding protein 4 3 0.832 0.714 1.206 0.942 1.042 0.973 1.126 2.37 2.01 166048.3 CADM3 Isoform 1 of Cell adhesion molecule 3 1 0.910 0.924 1.012 1.537 1.418 1.110 1.224 2.04 2.31 167313.2 CCDC38 Coiled-coil domain-containing protein 38 1 0.711 1.037 0.867 0.883 0.950 0.837 0.912 1.97 1.54 176920.7 NPHP4 Nephrocystin-4 1 1.498 0.836 1.128 1.665 1.157 0.884 0.523 3.2 5.77 179330.6 UBB;RPS27A ubiquitin and ribosomal protein S27a precursor 1 1.078 0.842 1.192 1.326 1.866 1.306 1.227 2 8.53 218803.3 FBLN1 Isoform B of Fibulin-1 6 0.912 0.880 0.808 1.407 0.891 1.002 1.020 2 5.42 220019.1 TREX1;ATRIP Isoform 1 of Three prime repair exonuclease 1 1 1.089 1.276 1.383 1.881 1.661 1.056 1.305 2.8 2.64 220815.1 EFEMP1 EGF-containing fibulin-like extracellular matrix protein 1 1 1.117 1.107 0.958 1.175 1.278 1.221 1.221 2.03 2.16 301143.5 PI16 Isoform 1 of Peptidase inhibitor 16 1 0.870 0.986 1.036 1.428 0.912 0.989 1.247 16.63 35.33 306339.4 SPP1 osteopontin isoform b precursor 12 1.080 0.675 0.958 0.863 1.271 1.062 1.236 6.03 12.06 375705.4 SIRPB1 Signal-regulatory protein beta-1 isoform 3 3 1.292 0.674 1.082 1.125 1.583 1.202 1.375 1.76 0.69 418991.5 QSER1 Isoform 1 of Glutamine and serine-rich protein 1 1 0.942 0.919 1.014 1.061 0.994 1.015 1.157 1.7 0.98 419722.4 SEZ6L2, similar to seizure related 6 homolog-like 2 (SEZ6L2) 1 0.526 0.684 1.068 1.216 0.954 0.888 1.169 28.52 51.72 426051.3 IGHG2 Putative uncharacterized protein DKFZp686C15213 39 0.661 0.667 0.637 0.428 0.360 0.564 0.775 2.26 1.16 465296.2 XPO6 Exportin-6 1 0.899 1.042 1.006 1.006 1.016 1.198 1.200 1.7 1.55 479786.5 KHSRP KH-type splicing regulatory protein 1 1.016 0.851 0.858 0.714 1.029 0.967 0.034 9.23 24.62 480192.1 RBP4 Retinol binding protein 4, plasma 4 1.080 1.348 1.111 1.224 1.092 1.092 1.001 2 7.82 554634.1 CUTA Isoform B of Protein CutA 1 0.822 0.818 0.789 1.000 0.943 1.060 0.777 2 1.11 645500.3 C2 cDNA FLJ55526, highly similar to Complement C2 1 0.736 0.747 0.831 1.004 0.598 0.501 1.112 2 24.49 746802.1 Conserved hypothetical protein 1 0.810 0.870 0.601 0.670 1.059 0.942 0.176 6.94 9.24 797025.1 PRNP Major prion protein 3 0.818 0.813 0.967 1.012 1.166 1.006 1.148 1.56 1.03 829842.1 C14orf49 Isoform 2 of Nesprin-3 1 0.914 0.999 0.847 0.993 1.181 0.978 1.088 7.04 15.81 844060.2 NBL1 Neuroblastoma, suppression of tumorigenicity 1 3 1.047 0.750 1.113 0.963 1.168 1.005 1.164 5 7.33 879231.1 SERPINF2 Alpha-2-antiplasmin 2 0.979 1.012 0.820 1.511 0.883 0.924 0.657 2.09 0.38 879319.1 260 kDa protein 1 1.239 1.056 1.266 1.631 1.512 1.322 1.160 2.1 10.00 888695.1 IGHV1-69 similar to hCG1773549 2 1.630 0.892 0.641 1.212 0.820 1.004 0.971 8.01 4.19 896419.3 ITIH4 Isoform 1 of Inter-alpha-trypsin inhibitor heavy chain H4 4 1.027 1.201 1.010 0.972 1.211 1.097 0.993 4.06 5.12 914898.1 52 kDa protein 2 1.171 0.852 1.123 0.871 1.479 1.182 0.714 2.59 7.55 945490.1 RARRES2 Putative uncharacterized protein RARRES2 1 0.830 0.911 0.890 0.790 0.668 0.844 0.862 5.88 13.79 945846.1 PRSS1 28 kDa protein 11 0.949 1.215 1.395 1.948 2.392 1.651 1.926 1.4 7.73 946181.1 PECI Putative uncharacterized protein PECI 1 1.127 0.918 1.046 0.788 1.143 0.835 0.626 18.45 27.52 953689.1 AHSG Alpha-2-HS-glycoprotein 13 0.886 0.932 0.693 0.764 0.816 0.941 0.905 2.39 2.91 964977.1 NTM Isoform 2 of Neurotrimin 1 1.125 0.974 1.148 0.881 1.164 0.949 1.055 2 4.97 14964.5 LY6H lymphocyte antigen 6H isoform b 1 1.140 1.087 0.893 0.899 0.856 1.045 0.809 1.4 1.51 21727.1 C4BPA C4b-binding protein alpha chain 1 1.081 1.236 1.407 1.299 7.164 0.906 5.615 2 11.72 22445.1 PPBP Platelet basic protein 1 1.493 1.461 2.855 2.163 2.89 0.82 21033.2 COL3A1 Isoform 1 of Collagen alpha-1(III) chain 1 1.071 0.972 1.164 1.069 1.065 1.147 0.503 8.59 4.81 29751.1 CNTN1 Isoform 1 of Contactin-1 4 0.959 0.763 1.030 0.723 0.951 1.042 0.865 7.7 15.06 22426.1 AMBP Protein AMBP 5 1.173 1.174 1.399 1.008 1.145 1.690 0.923 2.01 4.27 220460.1 OSBPL2 Oxysterol-binding protein-related protein 2 1 1.018 1.035 1.066 1.097 0.896 1.019 0.748 8.01 24.84 22892.2 THY1 Thy-1 membrane glycoprotein 5 1.025 0.973 1.269 0.722 1.768 1.262 0.751 1.54 1.47 306903.9 PPP1R13B Apoptosis-stimulating of p53 protein 1 1 0.976 0.975 0.902 1.150 0.529 0.832 1.030 3.71 1.92 23814.2 NEO1 Isoform 1 of Neogenin 2 0.783 0.716 1.059 0.687 0.952 0.924 0.841 2 6.88 307189.3 IFNA21 Interferon alpha-21 1 1.111 0.772 1.194 0.799 0.552 0.821 1.092 4.04 2.40 24966.1 CNTN2 Contactin-2 2 0.859 0.840 0.771 0.624 1.366 0.781 1.002 1.71 1.26 329213.2 Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 1 2.392 2 5.31 26199.2 GPX3 Glutathione peroxidase 3 2 1.110 1.002 1.295 1.121 1.174 0.871 0.773 10.32 25.00 385896.1 SPP1 Isoform D of Osteopontin 8 1.085 0.716 0.870 0.771 0.985 0.921 0.799 2.08 3.64 27166.1 TIMP2 Metalloproteinase inhibitor 2 1 0.707 0.753 0.771 0.938 0.753 0.655 0.615 2.54 11.30 387107.3 IGKV2-40 Ig kappa chain V-II region Cum 1 1.432 1.348 1.202 1.631 1.016 1.175 1.026 10.68 12.78 29658.1 EFEMP1 EGF-containing fibulin-like extracellular matrix protein 6 0.894 0.948 1.099 0.764 0.987 0.995 0.781 2.67 7.03 456429.3 UBA52 ubiquitin and ribosomal protein L40 precursor 1 1.121 0.950 1.119 0.825 1.442 1.054 1.003 9.23 11.72 29863.4 55 kDa protein 4 1.205 1.132 1.605 1.169 1.263 1.323 1.009 1.42 1.73 464979.4 SUCLA2Succinyl-CoA ligase [ADP-forming] subunit beta 1 0.887 0.931 1.083 0.931 0.609 0.998 0.951 4.47 1.61 32291.2 C5 Complement C5 2 1.227 0.976 1.311 1.034 1.016 1.173 0.914 3.86 6.07 465436.4 CAT Catalase 2 1.030 1.058 1.037 1.136 1.604 0.952 1.086 4.07 11.80 32328.2 KNG1 Isoform HMW of Kininogen-1 10 1.486 0.935 1.117 0.796 0.780 0.835 1.057 2 1.17 470535.1 CACNA2D1 Dihydropyridine receptor alpha 2 subunit 1 1.160 0.707 0.824 2.23 0.78 44600.3 SORCS2 VPS10 domain-containing receptor SorCS2 1 0.946 1.013 1.152 1.009 1.467 0.739 0.838 1.73 3.08 556442.1 IGFBP2 Insulin-like growth factor binding protein 2 variant 1 1.264 1.153 1.290 1.262 1.524 1.316 1.224 2 2.26 152847.4 WFIKKN2 kunitz and NTR domain-containing protein 2 1 0.835 0.763 1.080 0.833 1.306 1.059 1.051 1.7 50.64 645363.2 IGHG1; IGHV4-31 Putative uncharacterized protein 74 1.206 1.198 0.863 1.264 1.512 1.055 1.015 19.03 40.60 154742.6 IGLV2-14;IGLC2 IGL@ protein 31 1.131 0.899 1.288 1.228 1.028 1.127 1.188 1.7 5.03 645788.2 PRKACB, similar to cAMP-dependent protein kinase 1 0.248 3.288 0.218 5.224 3.137 0.493 1.344 2 0.93 169244.1 PTH1R Seven transmembrane helix receptor 1 1.224 1.049 1.235 1.102 1.113 0.926 1.268 4.69 36.92 719373.2 IGLC1 IGL@ protein 20 1.366 1.668 0.772 3.207 1.067 1.262 1.399 2.03 2.06 176427.1 CADM4 Cell adhesion molecule 4 1 0.999 1.159 1.887 0.877 1.341 0.667 1.183 2.02 7.24 746581.3 C22orf36 of Leucine-rich repeat-containing protein 1 0.722 1.231 1.096 0.442 0.774 1.168 1.174 4.7 1.64 177543.6 PAM Peptidyl-glycine alpha-amidating monooxygenase 2 0.846 0.962 0.756 0.681 0.903 0.699 0.995 2.17 4.85 783862.2 BLVRB Flavin reductase 1 1.296 2.074 2.045 1.004 3.329 1.107 2.867 7.24 10.71 185662.4 CD99L2 Putative uncharacterized protein CD99L2 3 0.748 1.010 0.940 0.758 0.955 0.711 0.825 2 37.45 807428.1 - Putative uncharacterized protein 21 2.207 1.493 1.281 2.53 2.92 216172.2 LAMP2 lysosome-associated membrane glycoprotein 1 0.909 0.836 0.840 0.727 1.264 0.823 1.387 1.7 1.58 845432.1 C5orf33 Isoform 1 of UPF0465 protein C5orf33 1 1.726 1.458 1.084 3.183 1.681 1.068 1.143 16.11 30.33 218874.1 SPP1 Isoform B of Osteopontin 28 0.656 0.910 0.624 0.758 1.123 0.578 0.955 20.13 22.73 847179.1 APOA4 apolipoprotein A-IV precursor 8 0.942 1.260 0.888 0.895 0.829 0.788 1.063 2.6 4.49 219217.3 LDHB L-lactate dehydrogenase B chain 1 0.818 0.904 0.881 0.816 0.982 0.962 1.173 2.54 6.48 852617.1 NBL1 Isoform 2 of Neuroblastoma suppressor of tumorigenicity 1 1 0.827 0.871 0.866 0.769 1.085 0.914 0.366 2.1 3.31 219301.7 MARCKS Myristoylated alanine-rich C-kinase substrate 1 0.847 1.032 1.061 0.793 0.816 1.056 0.904 18.37 42.37 887169.2 IGLV1-44 Putative uncharacterized protein 22 1.554 1.399 1.204 2.429 1.230 1.157 1.340 1.36 3.86 219695.4 PTPN2 Tyrosine-protein phosphatase non-receptor type 2 1 0.958 1.013 1.082 0.840 0.897 0.821 0.770 2 17.53 910380.1 SPARCL1 cDNA FLJ54278, highly similar to SPARC-like protein 1 11 1.787 1.185 1.397 1.536 1.759 1.029 1.217 1.71 1.85 220293.1 ART3 Isoform 2 of Ecto-ADP-ribosyltransferase 3 1 0.943 1.067 1.080 0.831 1.372 0.648 0.941 4.01 2.19 922434.1 NELL2 protein kinase C-binding protein NELL2 isoform a 2 1.115 0.759 0.736 0.924 0.977 0.832 0.760 2 4.91 247243.5 VSTM2B V-set and transmembrane domain-containing protein 1 0.898 0.989 1.176 0.814 1.312 0.955 0.700 2 2.82 941204.1 WNT16 Protein Wnt 1 0.955 1.005 0.928 1.027 0.678 1.006 0.951 10.27 7.79 292530.1 ITIH1 Inter-alpha-trypsin inhibitor heavy chain H1 5 1.411 1.156 1.027 0.965 0.932 1.060 0.883 1.81 0.20 941677.1 TTN 632 kDa protein 1 1.009 1.156 1.021 1.435 0.916 1.118 0.953 2.17 2.39 295542.5 NUCB1 Nucleobindin-1 1 0.824 1.000 0.879 0.850 1.175 0.813 0.957 1.7 1.55 943889.1 LOC100129103 similar to hCG2038970 1 0.876 0.858 0.898 1.085 1.074 0.896 0.620 2.02 2.54 299778.2 PON3 Serum paraoxonase/lactonase 3 1 1.505 0.990 0.934 0.865 0.882 1.087 0.745 4.49 2.83 956122.1 CD44 CD44 antigen isoform 1 precursor 2 0.845 0.852 1.045 0.860 1.081 0.844 0.675 4.32 4.45 328609.3 SERPINA4 Kallistatin 2 0.938 0.833 1.009 0.904 0.829 1.359 0.705 4.65 22.27 966913.1 - Anti-(ED-B) scFV (Fragment) 3 1.170 1.362 1.075 1.414 0.905 0.870 0.949 1.64 3.00 334914.2 C1orf25 Isoform 1 of TRM1-like protein 1 1.094 1.175 1.087 1.077 1.217 0.942 1.063 2.01 5.58 967849.1 C1QB Putative uncharacterized protein C1QB 1 2.145 20.15 30.57 386879.1 IGHA1, similar to Homo sapiens SNC73 protein (SNC73) mRNA 16 1.358 0.909 1.723 1.049 1.059 1.172 1.019 1.32 0.6843 879665.1 SEZ6L Seizure related 6 homolog (Mouse)-like 1 1.042 0.696 0.620 0.520 0.685 0.876 0.527 1.45 0.45 401776.9 MUC6 mucin-6 1 1.073 1.147 0.781 1.240 1.233 1.029 1.065 12.33 36.13 4656.3 B2M Beta-2-microglobulin 11 0.786 0.867 0.822 0.783 1.076 0.682 0.900 4.25 2.01 414249.5 NRXN3 Isoform 1 of Neurexin-3-alpha 2 0.741 0.915 0.762 0.695 0.969 0.636 0.736 1.51 0.92 4859.1 BLM Bloom syndrome protein 1 1.006 0.920 1.013 1.049 1.054 2.072 1.113 5.72 11.71 442298.1 NTM Isoform 3 of Neurotrimin 3 0.755 0.857 0.895 0.645 1.104 0.957 0.864 7.05 10.42 9619.1 CADM3 Isoform 2 of Cell adhesion molecule 3 3 0.702 0.837 0.708 0.806 0.771 0.699 1.007 5.06 5.57 451626.1 CRTAC1 Isoform 3 of Cartilage acidic protein 1 2 0.910 0.975 1.498 0.920 1.246 0.775 0.697 4.11 4.01 11218.1 CSF1R Macrophage colony-stimulating factor 1 receptor 2 0.926 0.940 1.235 0.825 1.165 0.819 0.575 2.43 4.14 464990.1 GP1BB Isoform 2 of Platelet glycoprotein Ib beta chain 1 0.878 1.068 1.073 0.869 0.908 0.697 0.563 1.74 1.79 11237.3 NARF Isoform 2 of Nuclear prelamin A recognition factor 1 0.874 1.080 1.062 1.012 1.171 1.411 0.641 1.52 2.09 465113.2 EXD2, Exonuclease 3'-5' domain-like-containing protein 2 1 1.040 1.241 1.091 1.402 1.027 1.213 1.466 2.42 2.23 12119.1 DCN Isoform A of Decorin 1 0.947 1.031 1.081 0.842 1.008 0.901 1.055 4.08 9.43 470652.1 Single-chain Fv (Fragment) 2 1.292 0.931 1.087 1.115 1.057 1.286 1.039 2.01 2.72 12303.4 SELENBP1 Selenium binding protein 1 1 0.612 0.606 1.087 0.659 1.279 1.182 0.706 2.44 5.93 477992.1 C1QB Complement C1q subcomponent subunit B 1 0.808 1.091 0.841 0.793 0.818 0.796 0.976 2.01 1.65 14371.1 CDH18 Cadherin-18 1 0.627 0.962 0.509 0.933 0.858 0.548 0.930 3.86 2.11 479514.2 CACNA2D1 Voltage-dependent calcium channel subunit alpha 2 0.810 1.069 1.251 0.730 1.253 0.636 0.890 2.03 2.44 16150.1 SERPINI1 Neuroserpin 1 1.048 0.812 1.217 0.847 1.386 1.246 0.496 3.52 12.20 513935.1 C8G Complement component 8, gamma polypeptide 2 0.847 1.142 1.056 0.903 1.035 1.017 1.073 1.72 1.55 16334.2 MCAM Isoform 1 of Cell surface glycoprotein MUC18 1 0.729 1.063 1.501 0.956 1.087 0.887 1.237 2.02 3.47 514438.1 NPDC1 Neural proliferation, differentiation and control, 1 1 0.791 0.884 0.975 0.648 0.986 0.810 0.214 2.07 3.23 16801.1 GLUD1 Glutamate dehydrogenase 1, mitochondrial 1 1.206 3.490 0.820 1.419 1.926 1.315 1.266 1.53 4.10 607636.4 KIF6 KIF6 protein 1 1.038 1.145 1.059 1.370 1.048 0.768 1.016 1.4 2.72 17087.2 ZBTB26 Zinc finger and BTB domain-containing protein 26 1 1.224 1.576 1.502 1.610 1.241 1.656 1.226 2.01 1.78 643663.1 PCSK2 Proprotein convertase subtilisin/kexin type 2, isoform CRA_b 1 0.956 1.890 3.881 1.098 2.509 1.229 1.752 3.1 7.36 19176.3 RARRES2 Retinoic acid receptor responder protein 2 1 1.215 1.869 1.070 0.924 1.004 1.006 1.068 1.73 1.19 644131.1 MAN2B1 lysosomal alpha-mannosidase isoform 2 precursor 1 0.992 1.014 0.863 0.892 0.764 0.840 0.895 36.05 12.64 19591.2 cDNA FLJ55673, highly similar to Complement factor B 19 1.115 1.130 0.824 1.112 0.835 0.959 1.001 7.54 4.17 645038.1 ITIH2 Inter-alpha (Globulin) inhibitor H2 3 1.303 0.907 0.977 0.939 0.844 0.954 0.938 26.77 20.77 20012.2 APLP1 Isoform 1 of Amyloid-like protein 1 23 0.936 1.034 0.943 0.767 1.031 0.748 0.986 2.05 1.76 645849.1 ECM1 Isoform 4 of Extracellular matrix protein 1 1 1.512 1.054 1.485 0.896 1.329 2.724 0.912 1.7 3.71 20602.1 CSNK2A2 Casein kinase II subunit alpha' 1 1.521 1.267 1.329 1.708 1.271 1.779 1.641 1.46 6.02 646304.4 PPIB Peptidyl-prolyl cis-trans isomerase B 1 0.718 0.961 0.901 0.757 1.061 1.184 0.876 2 65.40 647027.1 CHGB 32 kDa protein 33 0.201 0.113 0.007 0.478 0.078 0.321 0.424 388.41 88.18 745872.2 ALB Isoform 1 of Serum albumin 703 0.979 0.986 1.110 1.136 0.975 0.999 0.874 19.67 10.10 783390.2 CHL1 Isoform 1 of Neural cell adhesion molecule L1 protein 10 0.880 0.902 1.063 0.799 1.121 0.796 0.867 2.36 0.36 784473.2 VPS13D Vacuolar protein sorting-associated protein 13D 1 1.111 1.901 0.801 1.775 0.855 1.116 3.4 17.65 784990.2 UBB;RPS27A;UBC Ubiquitin C splice variant 2 0.956 1.203 1.002 0.806 1.231 1.364 0.634 2.05 2.76 788737.1 GAPDH 39 kDa protein 1 1.016 0.951 0.884 1.002 0.840 1.373 1.134 1.7 2.46 791964.4 ALCAM Activated leukocyte cell adhesion molecule 1 1.425 1.215 1.896 1.048 1.047 1.147 0.897 2.3 3.35 796333.1 ALDOA 45 kDa protein 1 0.775 0.971 0.860 0.773 1.039 1.281 1.077 1.71 5.56 816555.3 LOC100293440 similar to Ig lambda chain 2 0.928 1.248 1.261 1.138 0.981 1.126 0.984 2.11 6.51 844060.2 NBL1 Neuroblastoma, suppression of tumorigenicity 1 1 0.597 0.849 1.045 0.611 1.071 0.515 0.021 1.32 1.58 872653.3 LONRF1 LON peptidase N-terminal domain 1 1.079 0.968 0.957 1.081 1.274 1.099 1.273 1.4 1.86 879166.1 MTA1 PRIME end of clone of HeLa cells of Homo sapiens 1 1.549 0.860 1.043 1.026 0.827 4.028 0.753 4.82 4.30 879947.1 55 kDa protein 2 0.732 0.988 0.889 0.780 1.374 0.592 1.030 117.77 41.28 892604.1 C4B Complement component C4B (Childo blood group) 2 97 1.012 1.136 1.240 0.887 0.995 0.798 1.128 2.12 2.93 894498.1 ACTB Beta actin variant (Fragment) 1 1.172 3.033 0.977 1.480 1.167 1.240 0.992 2.08 2.93 908368.1 FSTL1; similar to Follistatin-related protein 1 1 0.910 0.787 1.163 1.009 0.844 1.704 0.181 2 27.21 910886.1 SPARCL1 , moderately similar to SPARC-like protein 1 27 1.265 2.640 1.752 0.933 4.248 0.734 1.544 1.46 3.95 924713.1 PCYT1A Putative uncharacterized protein PCYT1A 1 1.279 1.106 1.870 1.036 2.271 1.515 1.605 1.52 18.84 927226.1 ANLN Protein 1 0.986 0.887 1.008 0.948 1.140 1.247 1.233 2.01 2.99 936772.1 GOLM1 Isoform 1 of Golgi membrane protein 1 1 0.681 0.858 0.763 0.752 0.850 0.910 0.682 2.02 1.70 936846.1 IGLV3-27 similar to hCG2040019 2 1.089 1.170 1.250 0.959 0.994 1.272 1.112 1.41 37.63 937598.2 LOC100294156 similar to C4A protein isoform 2 88 1.508 0.931 1.657 0.843 1.232 1.012 0.302 2.01 6.09 939673.1 OPCML similar to Opioid-binding protein/cell adhesion 1 0.745 0.747 0.725 0.810 1.034 0.393 0.535 17.1 28.86 940990.1 DKK3 Dickkopf-related protein 3 14 0.771 0.874 0.829 0.776 0.956 1.024 0.971 10.87 11.07 941899.1 PKM2 66 kDa protein 5 0.851 1.049 1.158 0.850 1.073 0.749 1.070 3.43 0.34 943326.1 HSPG2 heparan sulfate proteoglycan core protein variant 1 0.977 1.051 0.959 0.812 0.950 2.302 0.773 1.44 2.71 965050.1 PET112L Putative uncharacterized protein PET112L 1 0.980 0.961 1.105 1.064 0.487 1.365 0.000 4.59 4.39 965868.1 TGFBI Transforming growth factor, beta-induced 2 0.680 0.953 0.897 0.955 0.811 0.888 0.774 4.56 4.724 656113.2 SIRPA Signal-regulatory protein alpha 2 0.762 0.812 0.682 0.552 1.297 0.675 0.857 4.86 3.761 23673.1 LGALS3BP Galectin-3-binding protein 2 0.955 1.011 0.878 0.966 1.240 1.178 1.357 SI Table 5 STRING v9.1 enrichment analysis of 39 proteins dysregulated in at least 4 out of 17 delirium subjects. Enrichment in biological enrichment, molecular function, cellular component and KEGG pathway was explored. The categories shown have statistically significant enrichment with a p value of at least 0.05 using FDR.
STRING v9.1 BIOLOGICAL PROCESS ENRICHMENT No. non- Bonferroni FDR GO_id Term Genes Proteins GO term corrected p-value p-value p-value platelet effects GO:0002576 platelet 10 FGA, SERPINA1, TF, FGB, CLU, A2M, 7.49E-15 9.27E-11 9.27E-11 degranulation FN1, SCG3, APOA1, HRG GO:0030168 platelet activation 11 F2, TF, SERPINA1, FGA, FGB, CLU, 2.51E-12 6.20E-09 3.10E-08 A2M, FN1, SCG3, APOA1, HRG wounding GO:0009611 response to 19 TF, APOE, A2M, GSN, C3, HBB, 1.45E-13 8.98E-10 1.80E-09 wounding APOA1, HRG, HP, FGA, FGB, CLU, ORM2, SCG3, SERPINC1, APOD, APOA2, KLK6, APOH GO:0042060 wound healing 16 TF, SERPINA1, FGA, FGB, CLU, A2M, 2.59E-13 1.07E-09 3.21E-09 FN1, SCG3, GSN, SERPINC1, APOD, HBB, APOA1, KLK6, APOH, HRG GO:0061041 regulation of wound 5 FGA, F2, SERPINC1, APOE, HRG 2.56E-06 6.44E-04 3.17E-02 healing acute-phase, GO:0002526 acute inflammatory 8 F2, SERPINA1, HP, ORM2, FN1, 2.12E-12 6.20E-09 2.62E-08 inflammation response APOA2, SERPINA3, ORM1 GO:0006953 acute-phase response 7 F2, FN1, SERPINA1, HP, SERPINA3, 3.71E-12 7.66E-09 4.60E-08 ORM2, ORM1 GO:0006950 response to stress 20 TF, GSN, HBB, SCG3, SERPINC1, 1.09E-06 3.56E-04 1.35E-02 APOA2, AGT, APOH, HBA1, A2M, APOA1, NCAM1, HRG, HP, FGA, FGB, CLU, ORM2, CST3, KLK6 GO:0080134 regulation of 11 A2M, APOA1, HRG, HP, FGA, CLU, 2.60E-06 6.44E-04 3.22E-02 response to stress F2, SERPINC1, APOD, AGT, SERPINF1 coagulation GO:0007596 blood coagulation 13 TF, SERPINA1, FGA, FGB, CLU, A2M, 8.07E-11 1.23E-07 9.99E-07 FN1, SCG3, SERPINC1, HBB, APOA1, APOH, HRG GO:0050817 coagulation 13 TF, SERPINA1, FGA, FGB, CLU, A2M, 8.07E-11 1.23E-07 9.99E-07 FN1, SCG3, SERPINC1, HBB, APOA1, APOH, HRG GO:0007599 hemostasis 13 TF, SERPINA1, FGA, FGB, CLU, A2M, 8.95E-11 1.23E-07 1.11E-06 FN1, SCG3, SERPINC1, HBB, APOA1, APOH, HRG GO:0050878 regulation of body 13 TF, SERPINA1, FGA, FGB, CLU, A2M, 9.29E-10 8.85E-07 1.15E-05 fluid levels FN1, SCG3, SERPINC1, HBB, APOA1, APOH, HRG GO:0072378 blood coagulation, 4 FGA, F2, APOH, A2M 2.51E-07 1.15E-04 3.11E-03 fibrin clot formation GO:0030193 regulation of blood 5 FGA, F2, SERPINC1, APOE, HRG 4.70E-07 1.76E-04 5.81E-03 coagulation GO:0051918 negative regulation 3 HRG, F2, APOH 1.26E-06 3.89E-04 1.56E-02 of fibrinolysis GO:1900047 negative regulation 4 APOE, F2, APOH, HRG 1.38E-06 4.02E-04 1.70E-02 of hemostasis GO:0030195 negative regulation 4 APOE, F2, APOH, HRG 1.38E-06 4.02E-04 1.70E-02 of blood coagulation GO:0050819 negative regulation 4 APOE, F2, APOH, HRG 2.20E-06 5.81E-04 2.73E-02 of coagulation GO:0050818 regulation of 5 FGA, F2, SERPINC1, APOE, HRG 7.48E-07 2.65E-04 9.26E-03 coagulation enzyme activity GO:0070613 regulation of protein 10 F2, SERPINC1, APOE, SERPINA3, 1.28E-10 1.58E-07 1.58E-06 processing SERPINA1, CLU, A2M, AGT, SERPINF1, CST3 GO:0030162 regulation of 9 F2, SERPINC1, CLU, AGT, APOE, 4.29E-10 4.43E-07 5.31E-06 proteolysis SERPINF1, SERPINA3, SERPINA1, CST3 GO:0051346 negative regulation 9 SERPINC1, SERPINA3, SERPINA1, 2.37E-08 1.63E-05 2.93E-04 of hydrolase activity APOA2, A2M, AGT, APOA1, SERPINF1, CST3 GO:0010951 negative regulation 7 SERPINC1, A2M, AGT, SERPINF1, 1.46E-07 8.21E-05 1.81E-03 of endopeptidase SERPINA3, SERPINA1, CST3 activity GO:0010466 negative regulation 7 SERPINC1, A2M, AGT, SERPINF1, 1.53E-07 8.21E-05 1.89E-03 of peptidase activity SERPINA3, SERPINA1, CST3 GO:0043086 negative regulation 11 APOE, SERPINA3, SERPINA1, HP, 2.09E-07 1.05E-04 2.59E-03 of catalytic activity A2M, CST3, SERPINC1, APOA2, AGT, APOA1, SERPINF1 GO:0072376 protein activation 5 FGA, F2, CLU, A2M, APOH 3.96E-06 9.42E-04 4.90E-02 cascade extracellular GO:0006887 exocytosis 10 TF, SERPINA1, FGA, FGB, CLU, A2M, 3.12E-10 3.51E-07 3.86E-06 FN1, SCG3, APOA1, HRG GO:0032940 secretion by cell 11 TF, SERPINA1, FGA, FGB, CLU, A2M, 2.61E-09 2.31E-06 3.23E-05 FN1, SCG3, AGT, APOA1, HRG GO:0001775 cell activation 12 TF, SERPINA1, FGA, FGB, CLU, A2M, 5.43E-09 4.48E-06 6.72E-05 FN1, SCG3, F2, AGT, APOA1, HRG GO:0046903 secretion 11 TF, SERPINA1, FGA, FGB, CLU, A2M, 2.21E-08 1.61E-05 2.74E-04 FN1, SCG3, AGT, APOA1, HRG GO:0030198 extracellular matrix 8 FGA, FGB, A2M, AGT, FN1, TTR, 1.55E-06 4.37E-04 1.92E-02 organization NCAM1, CST3 GO:0043062 extracellular 8 FGA, FGB, A2M, AGT, FN1, TTR, 1.59E-06 4.37E-04 1.97E-02 structure NCAM1, CST3 organization biological GO:0065008 regulation of 22 GSN, HBB, TCF3, SCG3, SERPINC1, 1.64E-08 1.27E-05 2.03E-04 regulation biological quality CHGA, APOA2, APOH, A2M, TTR, APOA1, AZGP1, HRG, SERPINA3, SERPINA1, HP, FGA, FGB, CLU, FN1, NRCAM, KLK6 GO:0051241 negative regulation 9 F2, APOD, APOE, APOA2, AGT, 1.37E-07 8.21E-05 1.69E-03 of multicellular APOA1, CST3, APOH, HRG organismal process GO:0022603 regulation of 11 FGA, FGB, FN1, CST3, C3, F2, 2.24E-07 1.07E-04 2.77E-03 anatomical structure NRCAM, APOA1, SERPINF1, APOH, morphogenesis HRG GO:0051128 regulation of cellular 15 GSN, C3, APOA1, NCAM1, HRG, 6.28E-07 2.28E-04 7.77E-03 component FGA, FGB, CLU, FN1, CST3, F2, organization APOD, APOA2, AGT, KLK6 GO:0051234 establishment of 20 GSN, HBB, PTGDS, SCG3, APOA2, 1.40E-06 4.02E-04 1.73E-02 localization AGT, APOH, HBA1, A2M, TTR, AZGP1, HRG, SERPINA1, FGA, FGB, CLU, ORM2, FN1, ORM1, APOD GO:0044092 negative regulation 11 APOE, A2M, APOA1, SERPINA3, 2.08E-06 5.59E-04 2.57E-02 of molecular SERPINA1, HP, CST3, SERPINC1, function APOA2, AGT, SERPINF1 GO:0032101 regulation of 9 FGA, A2M, F2, SERPINC1, APOD, 3.74E-06 9.07E-04 4.63E-02 response to external AGT, APOA1, SERPINF1, HRG stimulus cholesterol, GO:0043691 reverse cholesterol 4 APOE, CLU, APOA1, APOA2 6.31E-08 4.11E-05 7.81E-04 lipoprotein transport GO:0010873 positive regulation 3 AGT, APOA1, APOA2 3.01E-07 1.24E-04 3.73E-03 of cholesterol esterification GO:0034384 high-density 3 APOE, APOA1, APOA2 3.01E-07 1.24E-04 3.73E-03 lipoprotein particle clearance GO:0034380 high-density 3 APOE, APOA1, APOA2 3.01E-07 1.24E-04 3.73E-03 lipoprotein particle assembly GO:0010872 regulation of 3 AGT, APOA1, APOA2 8.40E-07 2.89E-04 1.04E-02 cholesterol esterification GO:0033700 phospholipid efflux 3 APOE, APOA1, APOA2 1.26E-06 3.89E-04 1.56E-02 GO:0034374 low-density 3 APOE, AGT, APOA2 2.46E-06 6.35E-04 3.05E-02 lipoprotein particle remodeling regeneration GO:0014012 peripheral nervous 3 APOE, APOD, APOA1 1.51E-07 8.21E-05 1.87E-03 system axon regeneration GO:0031099 regeneration 6 APOD, APOE, APOA1, KLK6, GSN, 2.13E-07 1.05E-04 2.63E-03 APOA2 Vesicle, particle, GO:0016192 vesicle-mediated 12 TF, APOE, A2M, GSN, APOA1, HRG, 4.26E-07 1.70E-04 5.27E-03 granule transport SERPINA1, FGA, FGB, CLU, FN1, SCG3 GO:0006810 transport 20 GSN, HBB, PTGDS, SCG3, APOA2, 1.00E-06 3.35E-04 1.24E-02 AGT, APOH, HBA1, A2M, TTR, AZGP1, HRG, SERPINA1, FGA, FGB, CLU, ORM2, FN1, ORM1, APOD STRING v9.1 MOLECULAR FUNCTION ENRICHMENT No. non- Bonferroni FDR GO_id Term Proteins GO term Genes corrected p-value p-value p-value enzyme activity GO:0004867 serine-type 7 SERPINA1, SERPINC1, A2M, AGT, 1.40E-09 5.45E-06 5.45E-06 endopeptidase HRG, SERPINF1, SERPINA3 inhibitor activity GO:0061134 peptidase regulator 8 SERPINC1, AGT, FN1, SERPINF1, 8.29E-09 1.61E-05 3.21E-05 activity SERPINA3, CST3, C3, HRG GO:0004857 enzyme inhibitor 9 SERPINC1, SERPINA3, APOA2, AGT, 2.40E-08 3.10E-05 9.31E-05 activity APOA1, SERPINF1, CST3, C3, HRG GO:0004866 endopeptidase 7 SERPINC1, AGT, SERPINF1, 4.21E-08 3.45E-05 1.63E-04 inhibitor activity SERPINA3, CST3, C3, HRG GO:0030414 peptidase inhibitor 7 SERPINC1, AGT, SERPINF1, 5.33E-08 3.45E-05 2.07E-04 activity SERPINA3, CST3, C3, HRG GO:0061135 endopeptidase 7 SERPINC1, AGT, SERPINF1, 5.33E-08 3.45E-05 2.07E-04 regulator activity SERPINA3, CST3, C3, HRG GO:0002020 protease binding 5 SERPINA1, SERPINC1, CST3, A2M, 5.66E-07 3.14E-04 2.20E-03 FN1 GO:0030234 enzyme regulator 10 SERPINA3, FN1, CST3, C3, 7.73E-06 2.31E-03 3.00E-02 activity SERPINC1, APOA2, AGT, SERPINF1, APOH, HRG ligand binding GO:0005102 receptor binding 13 APOE, C3, FAM3C, TTR, APOA1, 8.70E-07 4.22E-04 3.38E-03 HRG, FGA, FGB, FN1, F2, CHGB, APOA2, AGT, GO:0031720 haptoglobin binding 2 HBA1, HBB 5.62E-06 1.82E-03 2.18E-02 cholesterol, GO:0017127 cholesterol 3 APOE, APOA1, APOA2 2.08E-06 8.98E-04 8.08E-03 lipoprotein transporter activity GO:0015248 sterol transporter 3 APOE, APOA1, APOA2 2.77E-06 1.08E-03 1.08E-02 activity GO:0070325 lipoprotein particle 3 APOE, APOA1, APOA2 1.02E-05 2.82E-03 3.95E-02 receptor binding antioxidant GO:0016209 antioxidant activity 4 APOE, HP, HBA1, HBB 4.68E-06 1.65E-03 1.82E-02 STRING v9.1 CELLULAR COMPONENT ENRICHMENT No. non- Bonferroni FDR GO_id Term Genes corrected Proteins GO term p-value p-value p-value vesicle, particle, GO:0072562 blood microparticle 20 FGA, F2, SERPINC1, TF, CLU, A2M, 1.98E-32 2.86E-29 2.86E-29 granule AGT, ORM2, APOE, FN1, APOA1, SERPINA3, HBA1, HBB, HP, GSN, C3, APOA2, HRG, ORM1 GO:0060205 cytoplasmic 14 FGA, SERPINA2, TF, HP, FGB, CLU, 9.40E-24 4.53E-21 1.36E-20 membrane-bounded A2M, APOE, FN1, SCG3, APOA1, vesicle lumen HRG, HBA1, HBB
GO:0031983 vesicle lumen 14 FGA, SERPINA1, TF, HP, FGB, CLU, 9.40E-24 4.53E-21 1.36E-20 A2M, APOE, FN1, SCG3, APOA1, HRG, HBA1, HBB GO:0034774 secretory granule 10 FGA, SERPINA1, TF, FGB, CLU, A2M, 1.14E-16 4.02E-14 1.65E-13 lumen FN1, SCG3, APOA1, HRG GO:0030141 secretory granule 13 TF, CHGA, CHGB, SERPINA1, FGA, 2.99E-14 7.22E-12 4.33E-11 FGB, CLU, A2M, FN1, SCG3, APOA1, KLK6, HRG, GO:0016023 cytoplasmic 18 TF, APOE, HBA1, A2M, FAM3C, HBB, 1.57E-13 3.25E-11 2.27E-10 membrane-bounded APOA1, HRG, SERPINA1, HP, FGA, vesicle FGB, CLU, FN1, CHGA, CHGB, SERPINF1, KLK6 GO:0031410 cytoplasmic vesicle 18 TF, APOE, HBA1, A2M, FAM3C, HBB, 4.88E-13 8.82E-11 7.06E-10 APOA1, HRG, SERPINA1, HP, FGA, FGB, CLU, FN1, CHGA, CHGB, SERPINF1, KLK6 GO:0031988 membrane-bounded 24 TF, GSN, HBB, CHGA, APOA2, APOE, 9.37E-13 1.51E-10 1.36E-09 vesicle HBA1, A2M, C3, FAM3C, APOA1, AZGP1, HRG, SERPINA3, SERPINA1, HP, FGA, FGB, CLU, FN1, CST3, APOD, CHGB, KLK6 GO:0031982 vesicle 24 TF, GSN, HBB, CHGA, APOA2, APOE, 1.70E-12 2.29E-10 2.46E-09 HBA1, A2M, C3, FAM3C, APOA1, AZGP1, HRG, SERPINA3, SERPINA1, HP, FGA, FGB, CLU, FN1, CST3, APOD, CHGB, KLK6 GO:0044433 cytoplasmic vesicle 14 TF, APOE, HBA1, SERPINA1, HP, 1.74E-12 2.29E-10 2.52E-09 part FGA, FGB, CLU, A2M, FN1, CHGA, HBB, APOA1, HRG GO:0031093 platelet alpha 7 FGA, SERPINA1, FGB, CLU, A2M, 1.47E-11 1.77E-09 2.13E-08 granule lumen FN1, HRG GO:0070062 extracellular 20 TF, GSN, HBB, APOA2, APOE, HBA1, 2.94E-11 2.84E-09 4.26E-08 vesicular exosome A2M, C3, APOA1, AZGP1, HRG, SERPINA3, SERPINA1, HP, FGA, CLU, FN1, CST3, APOD, SERPINF1 GO:0031091 platelet alpha 7 FGA, SERPINA1, FGB, CLU, A2M, 7.56E-11 6.83E-09 1.09E-07 granule FN1, HRG GO:0071682 endocytic vesicle 5 APOE, HBA1, HBB, HP, APOA1 2.28E-10 1.94E-08 3.30E-07 lumen GO:0030139 endocytic vesicle 6 TF, APOE, HBA1, HBB, HP, APOA1 6.06E-06 3.02E-04 8.76E-03 GO:0043233 organelle lumen 17 TF, HBB, SCG3, APOA2, APOE, 2.70E-05 1.30E-03 3.91E-02 HBA1, A2M, APOA1, HRG, SERPINA1, HP, FGA, FGB, CLU, FN1, F2, KLK6 extracellular GO:0005615 extracellular space 22 TF, HBA1, A2M, GSN, HBB, TTR, 1.39E-16 4.02E-14 2.01E-13 APOA1, PTGDS, AZGP1, HRG, HP, LRG1, FGA, CLU, FN1, SPARCL1, CST3, F2, SERPINC1, APOD, APOA2, AGT GO:0044421 extracellular region 22 TF, GSN, HBB, PTGDS, SPARCL1, 1.81E-09 1.38E-07 2.63E-06 part SERPINC1, APOA2, AGT, HBA1, A2M, TTR, APOA1, AZGP1, HRG, HP, LRG1, FGA, CLU, FN1, CST3, F2, APOD GO:0005576 extracellular region 22 HBB, SPARCL1, HBA1, A2M, 3.16E-07 1.99E-05 4.58E-04 NCAM1, AZGP1, LRG1, FGA, CLU, CST3, CHGB, KLK6, GSN, SCG3, SERPINC1, CHGA, APOA2, AGT, FAMC3, TTR, HRG, HP cholesterol, GO:0034364 high-density 5 APOE, CLU, APOH, APOA1, APOA2 1.73E-09 1.38E-07 2.51E-06 lipoprotein lipoprotein particle GO:0034361 very-low-density 4 APOE, APOH, APOA1, APOA2 1.20E-07 7.87E-06 1.73E-04 lipoprotein particle GO:0034385 triglyceride-rich 4 APOE, APOH, APOA1, APOA2 1.20E-07 7.87E-06 1.73E-04 lipoprotein particle GO:0034366 spherical high- 3 CLU, APOA1, APOA2 6.54E-07 3.78E-05 9.46E-04 density lipoprotein particle GO:0034358 plasma lipoprotein 4 APOH, APOA1, APOA2, CLU 1.12E-06 6.23E-05 1.62E-03 particle GO:0032994 protein-lipid 4 APOH, APOA1, APOA2, CLU 1.42E-06 7.59E-05 2.05E-03 complex GO:0042627 chylomicron 3 APOE, APOH, APOA2 2.55E-06 1.32E-04 3.69E-03 coagulation GO:0031838 haptoglobin- 3 HBA1, HP, HBB 1.18E-08 8.51E-07 1.70E-05 hemoglobin complex GO:0005577 fibrinogen complex 3 FGA, FGB, FN1 4.09E-07 2.47E-05 5.92E-04 STRING v9.1 KEGG PATHWAY ENRICHMENT No. non- Bonferroni FDR GO_id Term Proteins GO term Genes corrected p-value p-value p-value Coagulation hsa04610 Complement and 7 FGA, F2, SERPINA1, SERPINC1, FGB, 1.82E-09 4.31E-07 4.31E-07 coagulation cascades A2M, C3 Acute-phase hsa05143 African 3 APOA1, HBA1, HBB 1.84E-04 2.19E-02 4.37E-02 inflammation trypanosomiasis SI Table 6 STRING v9.1 enrichment analysis of 31 proteins which are significantly correlated with either cognition (MMSE score) or health status (APACHE III score, Sydney cohort only) in delirium subjects. These proteins are the same group that appears in Table 3 of the main manuscript. Enrichment in biological enrichment, molecular function and cellular component were explored. The categories shown have statistically significant enrichment with a p value of at least 0.05 using FDR. Enrichment in KEGG pathway was also explored, however no matches were identified which were significant with a p value of at least 0.05 using FDR.
STRING v9.1 BIOLOGICAL PROCESS ENRICHMENT No. non- Bonferroni FDR GO_id Term proteins Genes corrected GO term p-value p-value p-value platelet effects GO:0002576 platelet 6 SOD1, CLU, APP, SCG3, APOA1, 1.12E-08 1.22E-04 1.39E-04 degranulation SERPING1 GO:0030168 platelet activation 6 SOD1, SERPING1, CLU, SCG3, 2.45E-06 1.38E-03 3.03E-02 APOA1, APP cholesterol, GO:0043691 reverse cholesterol 4 APOE, CLU, APOA1, APOA2 2.04E-08 1.22E-04 2.53E-04 lipoprotein transport GO:0010873 positive regulation 3 AGT, APOA1, APOA2 1.31E-07 2.31E-04 1.62E-03 of cholesterol esterification GO:0034384 high-density 3 APOE, APOA1, APOA2 1.31E-07 2.31E-04 1.62E-03 lipoprotein particle clearance GO:0034380 high-density 3 APOE, APOA1, APOA2 1.31E-07 2.31E-04 1.62E-03 lipoprotein particle assembly GO:0010872 regulation of 3 AGT, APOA1, APOA2 3.65E-07 3.47E-04 4.52E-03 cholesterol esterification GO:0033700 phospholipid efflux 3 APOE, APOA1, APOA2 5.47E-07 4.30E-04 6.76E-03 GO:0034375 high-density 3 APOE, APOA1, APOA2 1.85E-06 1.09E-03 2.29E-02 lipoprotein particle remodeling GO:0034377 plasma lipoprotein 3 APOE, APOA1, APOA2 3.61E-06 1.86E-03 4.47E-02 particle assembly GO:0034374 low-density 3 APOE, AGT, APOA2 1.07E-06 6.98E-04 1.33E-02 lipoprotein particle remodeling GO:0019218 regulation of steroid 5 SOD1, AGT, IGFBP7, APOA1, APOA2 2.27E-07 2.56E-04 2.81E-03 metabolic process secretion GO:0032940 secretion by cell 9 SCG2, SERPING1, CLU, SCG3, APP, 3.83E-08 1.22E-04 4.74E-04 SOD1, CHI3L1, AGT, APOA1 GO:0046903 secretion 9 SCG2, SERPING1, CLU, SCG3, APP, 2.22E-07 2.56E-04 2.75E-03 SOD1, CHI3L1, AGT, APOA1 enzyme activity GO:0051346 negative regulation 8 SERPING1, PCSK1N, APOA2, AGT, 3.95E-08 1.22E-04 4.89E-04 of hydrolase activity APOA1, SERPINF1, CST3, APP GO:0070613 regulation of protein 7 APOE, CLEC3B, SERPING1, CLU, 1.61E-07 2.49E-04 1.99E-03 processing AGT, SERPINF1, CST3 GO:0010951 negative regulation 6 AGT, SERPINF1, SERPING1, CST3, 5.69E-07 4.30E-04 7.05E-03 of endopeptidase PCSK1N, APP activity GO:0010466 negative regulation 6 AGT, SERPINF1, SERPING1, CST3, 5.90E-07 4.30E-04 7.31E-03 of peptidase activity PCSK1N, APP GO:0043086 negative regulation 9 APOE, SERPING1, CST3, APP, 1.42E-06 8.78E-04 1.76E-02 of catalytic activity PCSK1N, APOA2, AGT, APOA1, SERPINF1 biological GO:0051241 negative regulation 8 SOD1, APOE, SERPING1, APOA2, 1.90E-07 2.56E-04 2.36E-03 regulation of multicellular AGT, APOA1, CST3, APOH organismal process GO:0040014 regulation of 5 SOD1, AGT, PCSK1N, APOE, APP 4.15E-07 3.67E-04 5.13E-03 multicellular organism growth response to GO:0009628 response to abiotic 11 APOE, IGFBP7, SOD3, TTR, APOA1, 3.01E-07 3.10E-04 3.72E-03 stimulus stimulus APP, SOD1, PCSK1N, APOA2, CHI3L1, AGT
GO:0009611 response to 11 APOE, APOA1, SCG2, SERPING1, 7.07E-07 4.86E-04 8.75E-03 wounding CLU, SCG3, APP, SOD1, APOA2, CHI3L1, APOH fibril organisation GO:0097435 fibril organization 3 APOE, CLU, CST3 2.94E-06 1.58E-03 3.64E-02 STRING v9.1 MOLECULAR FUNCTION ENRICHMENT No. non- Bonferroni FDR GO_id Term Genes corrected p-value p-value p-value ligand binding GO:0005539 glycosaminoglycan 6 APOE, CLEC3B, BCAN, APOH, APP, 8.66E-07 1.27E-03 3.36E-03 binding SOD3 GO:0008201 heparin binding 5 APOE, CLEC3B, APOH, APP, SOD3 4.83E-06 3.12E-03 1.87E-02 enzyme activity GO:0004857 enzyme inhibitor 7 SCG5, PCSK1N, APOA2, AGT, 9.62E-07 1.27E-03 3.73E-03 activity APOA1, SERPINF1, CST3 cholesterol, GO:0017127 cholesterol 3 APOE, APOA1, APOA2 9.82E-07 1.27E-03 3.81E-03 lipoprotein transporter activity GO:0015248 sterol transporter 3 APOE, APOA1, APOA2 1.31E-06 1.27E-03 5.07E-03 activity GO:0070325 lipoprotein particle 3 APOE, APOA1, APOA2 4.82E-06 3.12E-03 1.87E-02 receptor binding GO:0071813 lipoprotein particle 3 APOE, APOA1, APOA2 6.71E-06 3.25E-03 2.60E-02 binding GO:0071814 protein-lipid 3 APOE, APOA1, APOA2 6.71E-06 3.25E-03 2.60E-02 complex binding GO:0070653 high-density 2 APOA1, APOA2 1.03E-05 4.43E-03 3.98E-02 lipoprotein particle receptor binding STRING v9.1 CELLULAR COMPONENT ENRICHMENT No. non- Bonferroni FDR GO_id Term Genes corrected p-value p-value p-value extracellular GO:0031012 extracellular matrix 10 SOD1, CLEC3B, CRTAC1, BCAN, 3.85E-10 3.73E-07 5.57E-07 IGFBP7, CLU, CHI3L1, SERPINF1, SPARCL1, APOH GO:0005615 extracellular space 13 CLEC3B, IGFBP7, TTR, APOA1, 2.70E-08 7.07E-06 3.90E-05 PTGDS, SCG2, CLU, SPARCL1, CST3, SOD1, PCSK1N, APOA2, AGT GO:0005576 extracellular region 19 SPARCL1, APP, SOD1, CLEC3B, 3.42E-07 4.13E-05 4.95E-04 IGFBP7, NCAM1, SCG2, CLU, CST3, SCG5, CRTAC1, SCG3, CHGA, PCSL1N, APOA2, AGT, FAM3C, TTR GO:0044421 extracellular region 16 PTGDS, CRTAC1, BCAN, SPARCL1, 1.53E-06 1.30E-04 2.22E-03 part APP, SOD1, PCSK1N, APOA2, AGT, CLEC3B, IGFBP7, TTR, APOA1, SCG2, CLU, CST3 cholesterol, GO:0034364 high-density 5 APOE, CLU, APOH, APOA1, APOA2 5.16E-10 3.73E-07 7.46E-07 lipoprotein lipoprotein particle GO:0034361 very-low-density 4 APOE, APOH, APOA1, APOA2 4.60E-08 8.33E-06 6.66E-05 lipoprotein particle GO:0034385 triglyceride-rich 4 APOE, APOH, APOA1, APOA2 4.60E-08 8.33E-06 6.66E-05 lipoprotein particle GO:0034366 spherical high- 3 CLU, APOA1, APOA2 3.22E-07 4.13E-05 4.66E-04 density lipoprotein particle GO:0034358 plasma lipoprotein 4 APOH, APOA1, APOA2, CLU 4.33E-07 4.82E-05 6.26E-04 particle GO:0032994 protein-lipid 4 APOH, APOA1, APOA2, CLU 5.48E-07 5.29E-05 7.94E-04 complex GO:0042627 chylomicron 3 APOH, APOE, APOA2 1.26E-06 1.14E-04 1.82E-03 vesicle, particle, GO:0060205 cytoplasmic 6 CLU, APOE, APP, SCG3, APOA1, 5.72E-09 2.07E-06 8.28E-06 granule membrane-bounded SERPING1 vesicle lumen GO:0031983 vesicle lumen 6 CLU, APOE, APP, SCG3, APOA1, 5.72E-09 2.07E-06 8.28E-06 SERPING1 GO:0030141 secretory granule 8 SCG2,SCG2, CHGA, SERPING1, 2.93E-08 7.07E-06 4.24E-05 PCSK1N, CLU, SCG3, APOA1, APP GO:0034774 secretory granule 5 CLU, APP, SCG3, APOA1, SERPING1 8.68E-08 1.40E-05 1.26E-04 lumen GO:0072562 blood microparticle 6 CLU, AGT, APOE, APOA1, 1.55E-07 2.25E-05 2.25E-04 SERPING1, APOA2 GO:0031410 cytoplasmic vesicle 11 APOE, FAM3C, APOA1, SCG2, 4.69E-07 4.85E-05 6.79E-04 SERPING1, CLU, APP, SOD1, CHGA, PCSK1N, SERPINF1 GO:0016023 cytoplasmic 10 APOE, FAM3C, APOA1, SCG2, 2.35E-06 1.89E-04 3.39E-03 membrane-bounded SERPING1, CLU, APP, CHGA, vesicle PCSK1N, SERPINF1