mDC Cell Maturation

## Warning: multiple methods tables found for 'grep'
## Warning: multiple methods tables found for 'grepl'
## Warning: replacing previous import by 'S4Vectors::grepl' when loading
## 'IRanges'
## Warning: replacing previous import by 'S4Vectors::grep' when loading
## 'IRanges'
## Warning: replacing previous import by 'S4Vectors::grepl' when loading
## 'AnnotationDbi'
## Warning: replacing previous import by 'S4Vectors::grep' when loading
## 'AnnotationDbi'
## Warning: replacing previous import by 'S4Vectors::grepl' when loading
## 'GenomeInfoDb'
## Warning: replacing previous import by 'S4Vectors::grep' when loading
## 'GenomeInfoDb'
## Version Okay
## (0.00153,0.279]   (0.279,0.445]   (0.445,0.633]   (0.633,0.845] 
##        1.207297        1.207297        1.207297        1.207297 
##    (0.845,1.08]     (1.08,1.36]     (1.36,1.66]     (1.66,2.01] 
##        1.207297        1.207297        1.207297        1.207297 
##      (2.01,2.4]      (2.4,2.84]     (2.84,3.34]      (3.34,3.9] 
##        1.207297        1.207297        1.278617        1.294579 
##      (3.9,4.54]     (4.54,5.26]     (5.26,6.07]     (6.07,6.99] 
##        1.420138        1.420138        1.653459        2.730194 
##     (6.99,10.5] 
##        4.296567

Fit zlm to stimulation and timepoint

Test for any time effect in LPS

In the LPS stimulation, testing for any time effect, when adjusting for ngeneson we detect 1359 differentially expressed genes. When we don’t adjust for ngeneson, we detect 1996 genes.

Gene set enrichment analysis

##  [1] "(Intercept)"    "cngeneson"      "StimPAM"        "StimPIC"       
##  [5] "StimLPS:Time2h" "StimPAM:Time2h" "StimPIC:Time2h" "StimLPS:Time4h"
##  [9] "StimPAM:Time4h" "StimPIC:Time4h" "StimLPS:Time6h" "StimPAM:Time6h"
## [13] "StimPIC:Time6h"
##           coefficient           module            P         Z       cont_P
##     1: StimLPS:Time2h   CORE_ANTIVIRAL 2.255322e-28 11.047449 4.702541e-10
##     2: StimLPS:Time2h       GO:0000002 3.119439e-02 -2.154584 8.465066e-03
##     3: StimLPS:Time2h       GO:0000009 2.448368e-01 -1.162982 5.874596e-01
##     4: StimLPS:Time2h       GO:0000026 2.448368e-01 -1.162982 5.874596e-01
##     5: StimLPS:Time2h       GO:0000028 2.414226e-01 -1.171438 2.259393e-01
##    ---                                                                    
## 25394: StimPIC:Time6h       GO:2001241 2.427907e-04  3.669747 4.015525e-02
## 25395: StimPIC:Time6h       GO:2001243 4.023620e-02  2.051316 7.727905e-02
## 25396: StimPIC:Time6h       GO:2001244 1.374592e-01  1.485320 4.417704e-03
## 25397: StimPIC:Time6h    PEAKED_INFLAM 4.596063e-05  4.075272 3.953161e-03
## 25398: StimPIC:Time6h SUSTAINED_INFLAM 2.714891e-70 17.724464 4.591031e-17
##            cont_Z       disc_P     disc_Z         adjp
##     1:  6.8375075 1.855746e-14  8.7859450 3.535844e-26
##     2: -2.6846307 7.177675e-01 -0.3624115 8.505368e-02
##     3: -0.5442115 2.734897e-01 -1.1004936 3.852028e-01
##     4: -0.5442115 2.734897e-01 -1.1004936 3.852028e-01
##     5: -1.2176058 6.615149e-01 -0.4390582 3.831804e-01
##    ---                                                
## 25394:  2.0787757 2.395321e-03  3.1110302 4.982239e-03
## 25395:  1.7838120 2.664162e-01  1.1171867 1.854072e-01
## 25396:  2.9088372 4.206981e-01 -0.8082781 3.922243e-01
## 25397:  2.9421606 5.617229e-03  2.8211440 1.179099e-03
## 25398:  9.8331320 1.204056e-30 15.2330452 7.661423e-67
##           coefficient             GOID             P         Z
##     1: StimLPS:Time2h   CORE_ANTIVIRAL  2.255322e-28 11.047449
##     2: StimLPS:Time4h   CORE_ANTIVIRAL  0.000000e+00 44.419672
##     3: StimLPS:Time6h   CORE_ANTIVIRAL  0.000000e+00 42.019192
##     4: StimPAM:Time2h   CORE_ANTIVIRAL  5.450429e-04  3.457584
##     5: StimPAM:Time4h   CORE_ANTIVIRAL  1.693595e-20  9.280075
##    ---                                                        
## 25394: StimPAM:Time4h SUSTAINED_INFLAM 3.786028e-156 26.621909
## 25395: StimPAM:Time6h SUSTAINED_INFLAM 4.990566e-173 28.042072
## 25396: StimPIC:Time2h SUSTAINED_INFLAM  1.992389e-31 11.662028
## 25397: StimPIC:Time4h SUSTAINED_INFLAM  2.442928e-45 14.131102
## 25398: StimPIC:Time6h SUSTAINED_INFLAM  2.714891e-70 17.724464
##              cont_P    cont_Z       disc_P     disc_Z          adjp
##     1: 4.702541e-10  6.837508 1.855746e-14  8.7859450  3.535844e-26
##     2: 3.085647e-42 21.975989 2.500349e-73 40.8429134  0.000000e+00
##     3: 3.526389e-44 23.086788 1.069596e-65 36.3373227  0.000000e+00
##     4: 9.787409e-06  4.617583 7.859410e-01  0.2721786  4.841903e-03
##     5: 6.183786e-11  7.173364 3.233500e-08  5.9506434  2.430166e-18
##    ---                                                             
## 25394: 4.187826e-42 20.481303 1.392422e-33 17.1677623 1.602626e-152
## 25395: 1.190721e-37 18.780511 3.688710e-42 20.8769678 4.225013e-169
## 25396: 2.116803e-09  6.470005 2.433396e-17 10.0225939  1.405630e-28
## 25397: 3.426867e-15  8.952578 1.840406e-19 11.0318174  2.297981e-42
## 25398: 4.591031e-17  9.833132 1.204056e-30 15.2330452  7.661423e-67
##                    TERM    Stim effectfilter include_sub
##     1:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE
##     2:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE
##     3:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE
##     4:   CORE_ANTIVIRAL StimPAM        FALSE       FALSE
##     5:   CORE_ANTIVIRAL StimPAM         TRUE        TRUE
##    ---                                                  
## 25394: SUSTAINED_INFLAM StimPAM         TRUE        TRUE
## 25395: SUSTAINED_INFLAM StimPAM         TRUE        TRUE
## 25396: SUSTAINED_INFLAM StimPIC         TRUE        TRUE
## 25397: SUSTAINED_INFLAM StimPIC         TRUE        TRUE
## 25398: SUSTAINED_INFLAM StimPIC         TRUE        TRUE
##           coefficient             GOID             P         Z
##     1: StimLPS:Time2h   CORE_ANTIVIRAL  2.255322e-28 11.047449
##     2: StimLPS:Time4h   CORE_ANTIVIRAL  0.000000e+00 44.419672
##     3: StimLPS:Time6h   CORE_ANTIVIRAL  0.000000e+00 42.019192
##     4: StimPAM:Time2h   CORE_ANTIVIRAL  5.450429e-04  3.457584
##     5: StimPAM:Time4h   CORE_ANTIVIRAL  1.693595e-20  9.280075
##    ---                                                        
## 25394: StimPAM:Time4h SUSTAINED_INFLAM 3.786028e-156 26.621909
## 25395: StimPAM:Time6h SUSTAINED_INFLAM 4.990566e-173 28.042072
## 25396: StimPIC:Time2h SUSTAINED_INFLAM  1.992389e-31 11.662028
## 25397: StimPIC:Time4h SUSTAINED_INFLAM  2.442928e-45 14.131102
## 25398: StimPIC:Time6h SUSTAINED_INFLAM  2.714891e-70 17.724464
##              cont_P    cont_Z       disc_P     disc_Z          adjp
##     1: 4.702541e-10  6.837508 1.855746e-14  8.7859450  3.535844e-26
##     2: 3.085647e-42 21.975989 2.500349e-73 40.8429134  0.000000e+00
##     3: 3.526389e-44 23.086788 1.069596e-65 36.3373227  0.000000e+00
##     4: 9.787409e-06  4.617583 7.859410e-01  0.2721786  4.841903e-03
##     5: 6.183786e-11  7.173364 3.233500e-08  5.9506434  2.430166e-18
##    ---                                                             
## 25394: 4.187826e-42 20.481303 1.392422e-33 17.1677623 1.602626e-152
## 25395: 1.190721e-37 18.780511 3.688710e-42 20.8769678 4.225013e-169
## 25396: 2.116803e-09  6.470005 2.433396e-17 10.0225939  1.405630e-28
## 25397: 3.426867e-15  8.952578 1.840406e-19 11.0318174  2.297981e-42
## 25398: 4.591031e-17  9.833132 1.204056e-30 15.2330452  7.661423e-67
##                    TERM    Stim effectfilter include_sub include
##     1:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE    TRUE
##     2:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE    TRUE
##     3:   CORE_ANTIVIRAL StimLPS         TRUE        TRUE    TRUE
##     4:   CORE_ANTIVIRAL StimPAM        FALSE       FALSE    TRUE
##     5:   CORE_ANTIVIRAL StimPAM         TRUE        TRUE    TRUE
##    ---                                                          
## 25394: SUSTAINED_INFLAM StimPAM         TRUE        TRUE    TRUE
## 25395: SUSTAINED_INFLAM StimPAM         TRUE        TRUE    TRUE
## 25396: SUSTAINED_INFLAM StimPIC         TRUE        TRUE    TRUE
## 25397: SUSTAINED_INFLAM StimPIC         TRUE        TRUE    TRUE
## 25398: SUSTAINED_INFLAM StimPIC         TRUE        TRUE    TRUE
##                                                                            TERM
##    1:                                                            CORE_ANTIVIRAL
##    2:                                                            CORE_ANTIVIRAL
##    3:                                                            CORE_ANTIVIRAL
##    4: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
##    5: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
##   ---                                                                          
## 3671:                                                             PEAKED_INFLAM
## 3672:                                                             PEAKED_INFLAM
## 3673:                                                          SUSTAINED_INFLAM
## 3674:                                                          SUSTAINED_INFLAM
## 3675:                                                          SUSTAINED_INFLAM
##                   GOID include    coefficient    Stim effectfilter
##    1:   CORE_ANTIVIRAL    TRUE StimLPS:Time2h StimLPS         TRUE
##    2:   CORE_ANTIVIRAL    TRUE StimLPS:Time4h StimLPS         TRUE
##    3:   CORE_ANTIVIRAL    TRUE StimLPS:Time6h StimLPS         TRUE
##    4:       GO:0000288    TRUE StimLPS:Time2h StimLPS         TRUE
##    5:       GO:0000288    TRUE StimLPS:Time4h StimLPS         TRUE
##   ---                                                             
## 3671:    PEAKED_INFLAM    TRUE StimLPS:Time4h StimLPS        FALSE
## 3672:    PEAKED_INFLAM    TRUE StimLPS:Time6h StimLPS        FALSE
## 3673: SUSTAINED_INFLAM    TRUE StimLPS:Time2h StimLPS         TRUE
## 3674: SUSTAINED_INFLAM    TRUE StimLPS:Time4h StimLPS         TRUE
## 3675: SUSTAINED_INFLAM    TRUE StimLPS:Time6h StimLPS         TRUE
##          variable        value component
##    1:           P 2.255322e-28         P
##    2:           P 0.000000e+00         P
##    3:           P 0.000000e+00         P
##    4:           P 6.098448e-14         P
##    5:           P 7.066308e-15         P
##   ---                                   
## 3671: include_sub 0.000000e+00   include
## 3672: include_sub 0.000000e+00   include
## 3673: include_sub 1.000000e+00   include
## 3674: include_sub 1.000000e+00   include
## 3675: include_sub 1.000000e+00   include
##                                                                            TERM
##    1:                                                            CORE_ANTIVIRAL
##    2:                                                            CORE_ANTIVIRAL
##    3:                                                            CORE_ANTIVIRAL
##    4: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
##    5: nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
##   ---                                                                          
## 3671:                                                             PEAKED_INFLAM
## 3672:                                                             PEAKED_INFLAM
## 3673:                                                          SUSTAINED_INFLAM
## 3674:                                                          SUSTAINED_INFLAM
## 3675:                                                          SUSTAINED_INFLAM
##                   GOID include    coefficient    Stim effectfilter
##    1:   CORE_ANTIVIRAL    TRUE StimLPS:Time2h StimLPS         TRUE
##    2:   CORE_ANTIVIRAL    TRUE StimLPS:Time4h StimLPS         TRUE
##    3:   CORE_ANTIVIRAL    TRUE StimLPS:Time6h StimLPS         TRUE
##    4:       GO:0000288    TRUE StimLPS:Time2h StimLPS         TRUE
##    5:       GO:0000288    TRUE StimLPS:Time4h StimLPS         TRUE
##   ---                                                             
## 3671:    PEAKED_INFLAM    TRUE StimLPS:Time4h StimLPS        FALSE
## 3672:    PEAKED_INFLAM    TRUE StimLPS:Time6h StimLPS        FALSE
## 3673: SUSTAINED_INFLAM    TRUE StimLPS:Time2h StimLPS         TRUE
## 3674: SUSTAINED_INFLAM    TRUE StimLPS:Time4h StimLPS         TRUE
## 3675: SUSTAINED_INFLAM    TRUE StimLPS:Time6h StimLPS         TRUE
##          variable        value component
##    1:           P 2.255322e-28         P
##    2:           P 0.000000e+00         P
##    3:           P 0.000000e+00         P
##    4:           P 6.098448e-14         P
##    5:           P 7.066308e-15         P
##   ---                                   
## 3671: include_sub 0.000000e+00   include
## 3672: include_sub 0.000000e+00   include
## 3673: include_sub 1.000000e+00   include
## 3674: include_sub 1.000000e+00   include
## 3675: include_sub 1.000000e+00   include
##                                TERM             GOID include
##    1:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    2:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    3:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    4: activation of MAPKKK activity       GO:0000185    TRUE
##    5: activation of MAPKKK activity       GO:0000185    TRUE
##   ---                                                       
## 4196:                 PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 4197:                 PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 4198:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 4199:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 4200:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
##          coefficient    Stim effectfilter    variable         value
##    1: StimPIC:Time2h StimPIC        FALSE           P  2.300405e-01
##    2: StimPIC:Time4h StimPIC         TRUE           P  6.968623e-48
##    3: StimPIC:Time6h StimPIC         TRUE           P 2.253407e-192
##    4: StimPIC:Time2h StimPIC         TRUE           P  1.295313e-06
##    5: StimPIC:Time4h StimPIC         TRUE           P  2.507901e-01
##   ---                                                              
## 4196: StimPIC:Time4h StimPIC        FALSE include_sub  0.000000e+00
## 4197: StimPIC:Time6h StimPIC        FALSE include_sub  0.000000e+00
## 4198: StimPIC:Time2h StimPIC         TRUE include_sub  1.000000e+00
## 4199: StimPIC:Time4h StimPIC         TRUE include_sub  1.000000e+00
## 4200: StimPIC:Time6h StimPIC         TRUE include_sub  1.000000e+00
##       component
##    1:         P
##    2:         P
##    3:         P
##    4:         P
##    5:         P
##   ---          
## 4196:   include
## 4197:   include
## 4198:   include
## 4199:   include
## 4200:   include
##                                TERM             GOID include
##    1:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    2:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    3:                CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    4: activation of MAPKKK activity       GO:0000185    TRUE
##    5: activation of MAPKKK activity       GO:0000185    TRUE
##   ---                                                       
## 4196:                 PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 4197:                 PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 4198:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 4199:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 4200:              SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
##          coefficient    Stim effectfilter    variable         value
##    1: StimPIC:Time2h StimPIC        FALSE           P  2.300405e-01
##    2: StimPIC:Time4h StimPIC         TRUE           P  6.968623e-48
##    3: StimPIC:Time6h StimPIC         TRUE           P 2.253407e-192
##    4: StimPIC:Time2h StimPIC         TRUE           P  1.295313e-06
##    5: StimPIC:Time4h StimPIC         TRUE           P  2.507901e-01
##   ---                                                              
## 4196: StimPIC:Time4h StimPIC        FALSE include_sub  0.000000e+00
## 4197: StimPIC:Time6h StimPIC        FALSE include_sub  0.000000e+00
## 4198: StimPIC:Time2h StimPIC         TRUE include_sub  1.000000e+00
## 4199: StimPIC:Time4h StimPIC         TRUE include_sub  1.000000e+00
## 4200: StimPIC:Time6h StimPIC         TRUE include_sub  1.000000e+00
##       component
##    1:         P
##    2:         P
##    3:         P
##    4:         P
##    5:         P
##   ---          
## 4196:   include
## 4197:   include
## 4198:   include
## 4199:   include
## 4200:   include
##                                   TERM             GOID include
##    1:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    2:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    3:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    4: ribosomal small subunit assembly       GO:0000028    TRUE
##    5: ribosomal small subunit assembly       GO:0000028    TRUE
##   ---                                                          
## 5519:                    PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 5520:                    PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 5521:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 5522:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 5523:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
##          coefficient    Stim effectfilter    variable        value
##    1: StimPAM:Time2h StimPAM        FALSE           P 5.450429e-04
##    2: StimPAM:Time4h StimPAM         TRUE           P 1.693595e-20
##    3: StimPAM:Time6h StimPAM         TRUE           P 2.878758e-98
##    4: StimPAM:Time2h StimPAM        FALSE           P 2.028658e-02
##    5: StimPAM:Time4h StimPAM         TRUE           P 2.348552e-07
##   ---                                                             
## 5519: StimPAM:Time4h StimPAM         TRUE include_sub 1.000000e+00
## 5520: StimPAM:Time6h StimPAM         TRUE include_sub 1.000000e+00
## 5521: StimPAM:Time2h StimPAM         TRUE include_sub 1.000000e+00
## 5522: StimPAM:Time4h StimPAM         TRUE include_sub 1.000000e+00
## 5523: StimPAM:Time6h StimPAM         TRUE include_sub 1.000000e+00
##       component
##    1:         P
##    2:         P
##    3:         P
##    4:         P
##    5:         P
##   ---          
## 5519:   include
## 5520:   include
## 5521:   include
## 5522:   include
## 5523:   include
##                                   TERM             GOID include
##    1:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    2:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    3:                   CORE_ANTIVIRAL   CORE_ANTIVIRAL    TRUE
##    4: ribosomal small subunit assembly       GO:0000028    TRUE
##    5: ribosomal small subunit assembly       GO:0000028    TRUE
##   ---                                                          
## 5519:                    PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 5520:                    PEAKED_INFLAM    PEAKED_INFLAM    TRUE
## 5521:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 5522:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
## 5523:                 SUSTAINED_INFLAM SUSTAINED_INFLAM    TRUE
##          coefficient    Stim effectfilter    variable        value
##    1: StimPAM:Time2h StimPAM        FALSE           P 5.450429e-04
##    2: StimPAM:Time4h StimPAM         TRUE           P 1.693595e-20
##    3: StimPAM:Time6h StimPAM         TRUE           P 2.878758e-98
##    4: StimPAM:Time2h StimPAM        FALSE           P 2.028658e-02
##    5: StimPAM:Time4h StimPAM         TRUE           P 2.348552e-07
##   ---                                                             
## 5519: StimPAM:Time4h StimPAM         TRUE include_sub 1.000000e+00
## 5520: StimPAM:Time6h StimPAM         TRUE include_sub 1.000000e+00
## 5521: StimPAM:Time2h StimPAM         TRUE include_sub 1.000000e+00
## 5522: StimPAM:Time4h StimPAM         TRUE include_sub 1.000000e+00
## 5523: StimPAM:Time6h StimPAM         TRUE include_sub 1.000000e+00
##       component
##    1:         P
##    2:         P
##    3:         P
##    4:         P
##    5:         P
##   ---          
## 5519:   include
## 5520:   include
## 5521:   include
## 5522:   include
## 5523:   include

PIC Stimulation GSEA

PAM Stimulation GSEA

Residuals within significant modules

PCA of core antiviral residuals

Module scores

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Visualization of residual correlation over time in LPS

## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.2831
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.7317
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.7317 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.3218 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.401 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.2831

Correlations accounting for ngeneson

## [1] 377
## [1] 534
## [1] 193
## [1] 362

PC plot of residuals in LPS

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Fit PAM and PIC

Visualization of residual correlation over time in PAM

## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.6551
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.4775
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.4775 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.6041 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.3993 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.6551
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Visualization of residual correlation over time in PIC

## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.8058
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.8955
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.8955 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.5383 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.3324 
## 
## Estimating optimal shrinkage intensity lambda (correlation matrix): 0.8058
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