Stimulated vs. Non-stimulated MAIT Cells

ZLM results

##       symbolid  I.x  I.y
##    1:      FOS    1    2
##    2:     IFNG    2    1
##    3:     CD52    3    5
##    4:   MTHFD2    4   13
##    5:     GZMB    5    4
##   ---                   
## 1487:    MYCBP 1487  694
## 1488:   FAM46C 1488 4696
## 1489:  THUMPD3 1489 4237
## 1490:    COPS8 1490 4036
## 1491:    UBE2W 1491 3857

We observe 1413 differentially expressed genes without the CDR effect in the model, and 291 with the CDR effect.

Analysis of deviance for ngeneson (Supplementary Figure 2)

## Mean % Deviance
dataset component V1
mdc C 1.650106
mdc D 4.869932
MAIT C 4.135422
MAIT D 5.282912
## % Deviance 90th Percentile
dataset component 90%
mdc C 4.392776
mdc D 9.364816
MAIT C 10.816661
MAIT D 13.380499

Visualization of most differentially expressed genes

Heatmap of MAITs based on most differentially expressed genes

Top 100 DE genes between stimulated and non-stimulated MAIT cells.

Some of the activated MAITs have transcriptional profiles more similar to unactivated MAITS.

GSEA

##                                             MAIT Activation [Up] 
##                                                    -0.3590160954 
##                                                proteasome (M226) 
##                                                    -0.2933650054 
##                               signaling in T cells\n(II) (M35.1) 
##                                                    -0.2654530340 
##               chaperonin mediated\nprotein folding (I)\n(M204.0) 
##                                                    -0.2180985181 
##                                               spliceosome (M250) 
##                                                    -0.2016985235 
##              chaperonin mediated\nprotein folding (II)\n(M204.1) 
##                                                    -0.1958057058 
##    respiratory electron\ntransport chain\n(mitochondrion) (M238) 
##                                                    -0.1931916437 
##    respiratory electron\ntransport chain\n(mitochondrion) (M219) 
##                                                    -0.1656004247 
##    respiratory electron\ntransport chain\n(mitochondrion) (M216) 
##                                                    -0.1633235288 
##             transcription\nelongation, RNA\npolymerase II (M234) 
##                                                    -0.1629657928 
##                                   translation initiation\n(M227) 
##                                                    -0.1528025990 
##    respiratory electron\ntransport chain\n(mitochondrion) (M231) 
##                                                    -0.1495440145 
##                           purine nucleotide\nbiosynthesis (M212) 
##                                                    -0.1473252342 
##                  translation initiation\nfactor 3 complex (M245) 
##                                                    -0.1470130188 
##                                   nuclear pore complex\n(M106.0) 
##                                                    -0.1436849298 
##                                  cell cycle, ATP binding\n(M144) 
##                                                    -0.1315680821 
##            mitotic cell cycle in\nstimulated CD4 T cells\n(M4.5) 
##                                                    -0.1300289382 
##                                    nucleotide metabolism\n(M181) 
##                                                    -0.1142870202 
##                              enriched for\nubiquitination (M138) 
##                                                    -0.1042517065 
##                                 enriched in T cells (II)\n(M223) 
##                                                    -0.0992421935 
##                                      golgi membrane (II)\n(M237) 
##                                                    -0.0982934396 
##                                cell cycle, mitotic\nphase (M230) 
##                                                    -0.0976745506 
##                                  intracellular transport\n(M147) 
##                                                    -0.0930669413 
##                                   T cell surface signature\n(S0) 
##                                                    -0.0922234313 
##               cell division - E2F\ntranscription network\n(M4.8) 
##                                                    -0.0886058705 
##                                 cytoskeletal remodeling\n(M32.8) 
##                                                    -0.0812717313 
##             enriched in NK cells\n(receptor activation)\n(M61.2) 
##                                                    -0.0733662231 
##                                  NK cell surface\nsignature (S1) 
##                                                    -0.0719236479 
##                        leukocyte activation and\nmigration (M45) 
##                                                    -0.0685381001 
##                  enriched in antigen\npresentation (II)\n(M95.0) 
##                                                    -0.0631207917 
##                        mitosis (TF motif\nCCAATNNSNNNGCG) (M169) 
##                                                    -0.0618164395 
##                              T cell differentiation\n(Th2) (M19) 
##                                                    -0.0566007808 
##                                   KLF12 targets network\n(M32.3) 
##                                                    -0.0542011145 
##                             enriched in monocytes\n(IV) (M118.0) 
##                                                    -0.0480880531 
##                                 enriched in NK cells (I)\n(M7.2) 
##                                                    -0.0409704177 
##                                signaling in T cells (I)\n(M35.0) 
##                                                    -0.0392371955 
##               small GTPase mediated\nsignal transduction\n(M215) 
##                                                    -0.0311426503 
##                                       E2F1 targets (Q4)\n(M10.1) 
##                                                    -0.0304191114 
##                                       cell adhesion (GO)\n(M117) 
##                                                    -0.0219926386 
##                   amino acid metabolishm\nand transport (M154.0) 
##                                                    -0.0113156747 
##                                innate antiviral\nresponse (M150) 
##                                                    -0.0108190609 
##                                            cell cycle (I) (M4.1) 
##                                                    -0.0001795511 
##                                      mitotic cell division\n(M6) 
##                                                     0.0002126170 
##                                       DC surface signature\n(S5) 
##                                                     0.0006536264 
##                                    PLK1 signaling events\n(M4.2) 
##                                                     0.0010094548 
##                                       blood coagulation\n(M11.1) 
##                                                     0.0046840658 
##                                                 DNA repair (M76) 
##                                                     0.0047458881 
##                 enriched in antigen\npresentation (III)\n(M95.1) 
##                                                     0.0048822238 
##                               double positive\nthymocytes (M126) 
##                                                     0.0056611267 
##                                     leukocyte migration\n(M88.0) 
##                                                     0.0084265132 
##                          regulation of signal\ntransduction (M3) 
##                                                     0.0091116959 
##                    T cell differentiation\nvia ITK and PKC (M18) 
##                                                     0.0118238187 
##                                    T cell differentiation\n(M14) 
##                                                     0.0132935877 
##                    phosphatidylinositol\nsignaling system (M101) 
##                                                     0.0135001279 
##             transcription regulation\nin cell development\n(M49) 
##                                                     0.0201527800 
##                          T cell activation and\nsignaling (M5.1) 
##                                                     0.0289074861 
##                               enriched in NK cells\n(II) (M61.0) 
##                                                     0.0331908671 
##                 cell division in\nstimulated CD4 T cells\n(M4.6) 
##                                                     0.0345433146 
##                                    MHC-TLR7-TLR8 cluster\n(M146) 
##                                                     0.0417165480 
##                         AP-1 transcription\nfactor network (M20) 
##                                                     0.1193520161 
## chemokines and\ninflammatory molecules\nin myeloid cells (M86.0) 
##                                                     0.1330329907 
##                             suppression of MAPK\nsignaling (M56) 
##                                                     0.1335629734 
##                              cell cycle and growth\narrest (M31) 
##                                                     0.1588741818 
##                                           MAIT Activation [Down] 
##                                                     0.3508645057

Figure 3 GSEA Results for MAIT Data Set

Figure 3

Figure 2 - Heatmap of Differentially Expressed Genes and Activated MAIT Module Scores

## RStudioGD 
##         2
## RStudioGD 
##         2

Figure 4 - Residual Correlations and PCA

Supplementary Figure 10 - Residual Background Correlation

## RStudioGD 
##         2

egid chrmap symbol
1831 Xq22.3 TSC22D3
5716 Xq22.3 PSMD10
122704 14q11.2 MRPL52
3002 14q11.2 GZMB
51102 1p35.3 MECR
93974 1p35.3 ATPIF1

Supplementary Figure 14

GSEA between non-stimulated and non-responding cells

PCA plots for ngeneson effect

## [1] 5.956767 3.843590

## RStudioGD 
##         2

Figure 1

Flow cytometry data

## mac version of flowJo workspace recognized.
## RStudioGD 
##         2
## RStudioGD 
##         2