AMP PD Targeted Proteomics Differential Expression Comparing Month 48 to Baseline
Project Lead:
Analysis Methodology
Note: The analysis that produced this target list is available to all registered AMP PD users in Terra and can be reused in your work.
Introduction
This analysis uses proteomics data described here.
Differential expression
Cohorts for DE were created by filtering for visit month = 0 and visit month = 48 and using the visit months as the groups for the t-test. Case and Control samples were separated into different data frames prior to the t-test.
Tools:
- R
- Olink Analyze Package
- olink_ttest
Input:
Underlying Analyses
Analysis Type:
Differential expression/T-test
Target Type:
Protein
Description:
Targeted proteomics data generated using the Olink Explore platform was analyzed using Olink provided analysis scripts within Terra. Data from release v3 was utilized, however, the data was reformatted by combining the separate Olink Explore panels into one file. Data has been uploaded into a community workspace google bucket for use. The proteomics data frame was combined with demographics and case/control info and was filtered to only contain samples at baseline for control and disease. Data was filtered to contain two timepoints, Month 48 and baseline Month 0. Data was then split by condition into two separate data frames. The two groups compared were “M0” and “M48.” The Olink ttest function was utilized and it performs a Welch 2-sample t-test at confidence level .95 for every protein within a given grouping variable. The function corrects for multiple testing using Benjamini-Hochberg (“fdr”).
Tissue Type:
CSF, Plasma
Source Data Type:
Proteomics
Source Data Cohorts:
Parkinson's Disease Biomarkers Program (PDBP), Parkinson's Progression Markers Initiative (PPMI)
Links:
Data Dictionary
| Field Name | Field Name Expanded | Short Description (optional) |
|---|---|---|
| Assay | Assay name | Olink protein assay for proximity extension assay |
| OlinkID | Unique Olink ID | Unique Olink ID |
| uniprot_id | Uniprot ID | Uniprot ID |
| ensembl_gene_id | ENSEMBL Gene ID | ENSEMBL Gene ID |
| Panel | Olink panel | Olink panel |
| estimate | Difference in mean NPX between groups | |
| Case | Case group | Average Expression for case group |
| Control | Control group | Average Expression for control group |
| Month_0 | Month zero time point | Average Expression for month zero time point |
| Month_48 | Month 48 time point | Average Expression for month 48 time point |
| statistic | Value of the t- statistic | |
| p_val | P value | P value for the test |
| parameter | Degrees of freedom for the t-statistic | |
| conf.low | Confidence low | Low bound of the confidence interval for the mean |
| conf.high | Confidence high | High bound of the confidence interval for the mean |
| method | Method that was used for analysis | |
| alternative | Description of the alternative hypothesis | |
| adj_p_val | Adjusted p value | Adjusted p value for the test (Benjamini & Hochberg) |
| Threshold | Text indication if assay is significant (adjust p-value < 0.05) | |
| Dataset | Dataset source | Data set source of D01 or D02 |
| Tissue | Tissue source | Sample tissue source: CSF or Plasma |
| Condition | Condition of the t-test: case or control | |
| gene_type | Gene type | Gene type from GENCODE |
| hgnc_symbol | HGNC symbol | HGNC symbol |
Nominated Targets
O15496 (protein)
ensembl_id: ENSG00000069764
hgnc_symbol: PLA2G10
gene_type: protein_coding
Assay:
PLA2G10
OlinkID:
OID21002
uniprot_id:
O15496
Panel:
Neurology
estimate:
-0.5188432749
Month_0:
0.4304111111
Month_48:
0.949254386
statistic:
-3.804666231
p_val:
0.0002335914128
parameter:
110.183106
conf.low:
-0.7890921021
conf.high:
-0.2485944476
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03696760431
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
PLA2G10
O43827 (protein)
ensembl_id: ENSG00000171819
hgnc_symbol: ANGPTL7
gene_type: protein_coding
Assay:
ANGPTL7
OlinkID:
OID21412
uniprot_id:
O43827
Panel:
Oncology
estimate:
-0.2541676236
Month_0:
0.2927393939
Month_48:
0.5469070175
statistic:
-4.286015251
p_val:
0.000037
parameter:
119.828409
conf.low:
-0.3715824054
conf.high:
-0.1367528418
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01814218988
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
ANGPTL7
O43854 (protein)
ensembl_id: ENSG00000164176
hgnc_symbol: EDIL3
gene_type: protein_coding
Assay:
EDIL3
OlinkID:
OID20081
uniprot_id:
O43854
Panel:
Cardiometabolic
estimate:
-0.2716215843
Month_0:
-0.1930373737
Month_48:
0.07858421053
statistic:
-4.126042684
p_val:
0.0000719
parameter:
110.1240196
conf.low:
-0.4020815735
conf.high:
-0.141161595
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01845801435
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
EDIL3
O75354 (protein)
ensembl_id: ENSG00000197586
hgnc_symbol: ENTPD6
gene_type: protein_coding
Assay:
ENTPD6
OlinkID:
OID20100
uniprot_id:
O75354
Panel:
Cardiometabolic
estimate:
-0.1718689527
Month_0:
0.5562959596
Month_48:
0.7281649123
statistic:
-3.433074748
p_val:
0.0008009814288
parameter:
129.9935199
conf.low:
-0.2709120416
conf.high:
-0.07282586377
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04950677412
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
ENTPD6
O75888 (protein)
ensembl_id: ENSG00000161955
hgnc_symbol: TNFSF13
gene_type: protein_coding
Assay:
TNFSF13
OlinkID:
OID20733
uniprot_id:
O75888
Panel:
Inflammation
estimate:
-0.2424087188
Month_0:
0.8694737374
Month_48:
1.111882456
statistic:
-4.091917623
p_val:
0.0000752
parameter:
127.9250435
conf.low:
-0.3596275368
conf.high:
-0.1251899007
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01845801435
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
TNFSF13
P07196 (protein)
ensembl_id: ENSG00000277586
hgnc_symbol: NEFL
gene_type: protein_coding
Assay:
NEFL
OlinkID:
OID20871
uniprot_id:
P07196
Panel:
Neurology
estimate:
-0.477169697
Month_0:
1.075030303
Month_48:
1.5522
statistic:
-4.159755056
p_val:
0.000065
parameter:
105.722736
conf.low:
-0.704602314
conf.high:
-0.2497370799
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01845801435
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
NEFL
P11464 (protein)
ensembl_id: ENSG00000231924
hgnc_symbol: PSG1
gene_type: protein_coding
Assay:
PSG1
OlinkID:
OID20916
uniprot_id:
P11464
Panel:
Neurology
estimate:
-0.72168958
Month_0:
-1.003780808
Month_48:
-0.2820912281
statistic:
-3.645720457
p_val:
0.0003852898394
parameter:
129.1039849
conf.low:
-1.113345945
conf.high:
-0.3300332153
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03709113792
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
PSG1
P13726 (protein)
ensembl_id: ENSG00000117525
hgnc_symbol: F3
gene_type: protein_coding
Assay:
F3
OlinkID:
OID21440
uniprot_id:
P13726
Panel:
Oncology
estimate:
-0.2603520999
Month_0:
0.7420373737
Month_48:
1.002389474
statistic:
-4.45804976
p_val:
0.0000189
parameter:
118.6439647
conf.low:
-0.3759943828
conf.high:
-0.1447098171
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01814218988
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
F3
P15514 (protein)
ensembl_id: ENSG00000109321
hgnc_symbol: AREG
gene_type: protein_coding
Assay:
AREG
OlinkID:
OID21357
uniprot_id:
P15514
Panel:
Oncology
estimate:
-0.3583449761
Month_0:
0.4474848485
Month_48:
0.8058298246
statistic:
-3.645022946
p_val:
0.0004237358393
parameter:
101.4328116
conf.low:
-0.5533569909
conf.high:
-0.1633329612
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03709113792
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
AREG
P16234 (protein)
ensembl_id: ENSG00000134853
hgnc_symbol: PDGFRA
gene_type: protein_coding
Assay:
PDGFRA
OlinkID:
OID20133
uniprot_id:
P16234
Panel:
Cardiometabolic
estimate:
-0.2282151515
Month_0:
0.4103848485
Month_48:
0.6386
statistic:
-3.613820383
p_val:
0.0004283623265
parameter:
131.4870304
conf.low:
-0.3531379125
conf.high:
-0.1032923906
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03709113792
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
PDGFRA
P18065 (protein)
ensembl_id: ENSG00000115457
hgnc_symbol: IGFBP2
gene_type: protein_coding
Assay:
IGFBP2
OlinkID:
OID20325
uniprot_id:
P18065
Panel:
Cardiometabolic
estimate:
-0.4390438065
Month_0:
0.9452737374
Month_48:
1.384317544
statistic:
-3.889147357
p_val:
0.0001582875301
parameter:
132.7888502
conf.low:
-0.6623380765
conf.high:
-0.2157495364
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.02912490553
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
IGFBP2
P20711 (protein)
ensembl_id: ENSG00000132437
hgnc_symbol: DDC
gene_type: protein_coding
Assay:
DDC
OlinkID:
OID20215
uniprot_id:
P20711
Panel:
Cardiometabolic
estimate:
-0.6633061138
Month_0:
1.650786869
Month_48:
2.314092982
statistic:
-4.305140806
p_val:
0.000032
parameter:
133.8222825
conf.low:
-0.9680394201
conf.high:
-0.3585728075
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.01814218988
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
DDC
P31997 (protein)
ensembl_id: ENSG00000124469
hgnc_symbol: CEACAM8
gene_type: protein_coding
Assay:
CEACAM8
OlinkID:
OID20102
uniprot_id:
P31997
Panel:
Cardiometabolic
estimate:
-0.2753504519
Month_0:
0.3374565657
Month_48:
0.6128070175
statistic:
-3.435700853
p_val:
0.000807175665
parameter:
122.6806167
conf.low:
-0.4339944829
conf.high:
-0.1167064208
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04950677412
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
CEACAM8
P56159 (protein)
ensembl_id: ENSG00000151892
hgnc_symbol: GFRA1
gene_type: protein_coding
Assay:
GFRA1
OlinkID:
OID21457
uniprot_id:
P56159
Panel:
Oncology
estimate:
-0.2097196704
Month_0:
0.5372838384
Month_48:
0.7470035088
statistic:
-3.462485535
p_val:
0.0007533822986
parameter:
114.5338257
conf.low:
-0.3297006142
conf.high:
-0.08973872657
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04950677412
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
GFRA1
P62736 (protein)
ensembl_id: ENSG00000107796
hgnc_symbol: ACTA2
gene_type: protein_coding
Assay:
ACTA2
OlinkID:
OID20079
uniprot_id:
P62736
Panel:
Cardiometabolic
estimate:
-0.3143806486
Month_0:
0.6977737374
Month_48:
1.012154386
statistic:
-3.509559208
p_val:
0.0006659257139
parameter:
103.5087374
conf.low:
-0.4920278722
conf.high:
-0.136733425
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04711235522
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
ACTA2
P80511 (protein)
ensembl_id: ENSG00000163221
hgnc_symbol: S100A12
gene_type: protein_coding
Assay:
S100A12
OlinkID:
OID21374
uniprot_id:
P80511
Panel:
Oncology
estimate:
-0.5422394471
Month_0:
-1.930679798
Month_48:
-1.388440351
statistic:
-3.744460059
p_val:
0.0002912223131
parameter:
108.473504
conf.low:
-0.8292660111
conf.high:
-0.2552128831
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03696760431
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
S100A12
Q07065 (protein)
ensembl_id: ENSG00000136026
hgnc_symbol: CKAP4
gene_type: protein_coding
Assay:
CKAP4
OlinkID:
OID20617
uniprot_id:
Q07065
Panel:
Inflammation
estimate:
-0.2458541733
Month_0:
0.6426282828
Month_48:
0.8884824561
statistic:
-3.692008112
p_val:
0.0003420160646
parameter:
114.7905475
conf.low:
-0.3777605055
conf.high:
-0.1139478411
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03709113792
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
CKAP4
Q12866 (protein)
ensembl_id: ENSG00000153208
hgnc_symbol: MERTK
gene_type: protein_coding
Assay:
MERTK
OlinkID:
OID20657
uniprot_id:
Q12866
Panel:
Inflammation
estimate:
-0.2276201489
Month_0:
0.8369868687
Month_48:
1.064607018
statistic:
-3.745392605
p_val:
0.0002829578153
parameter:
115.0991918
conf.low:
-0.3479994051
conf.high:
-0.1072408926
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.03696760431
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
MERTK
Q13261 (protein)
ensembl_id: ENSG00000134470
hgnc_symbol: IL15RA
gene_type: protein_coding
Assay:
IL15RA
OlinkID:
OID20498
uniprot_id:
Q13261
Panel:
Inflammation
estimate:
-0.2827808081
Month_0:
0.4928858586
Month_48:
0.7756666667
statistic:
-3.54878025
p_val:
0.0005462983288
parameter:
124.8054974
conf.low:
-0.4404876257
conf.high:
-0.1250739904
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04232374421
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
IL15RA
Q15043 (protein)
ensembl_id: ENSG00000104635
hgnc_symbol: SLC39A14
gene_type: protein_coding
Assay:
SLC39A14
OlinkID:
OID20852
uniprot_id:
Q15043
Panel:
Neurology
estimate:
-0.2215605529
Month_0:
0.7425131313
Month_48:
0.9640736842
statistic:
-3.500075511
p_val:
0.0006721191981
parameter:
110.3246245
conf.low:
-0.3470054592
conf.high:
-0.09611564658
method:
Welch Two Sample t-test
alternative:
two.sided
adj_p_val:
0.04711235522
Threshold:
Significant
Dataset:
D01
Tissue:
PLA
Condition:
Case
gene_name:
SLC39A14