cate that no enrichment was found for MixDTrees-MAP (or SOM). We included ... a higher enrichment for MixDTrees-MAP results, and values bellow it to SOM.
Cluster 1
Cluster 2 2
2
1.5
1.5
1.5
−0.5
0.5 0 −0.5 −1
−1
DPL
DPS
−2 DN2
SP4/SP8
DN3
DN4
DPL
DPS
−2.5 DN2
SP4/SP8
2
2
2
1.5
1.5
0
−1 −1.5 −2 DN3
DN4
DPL
DN3
DPS
0.5 0 −0.5
SP4/SP8
DPL
DPS
−2 DN2
SP4/SP8
−0.5 −1 −1.5
DN3
DN4
DPL
DPS
−2 DN2
SP4/SP8
DN3
DN4
DPL
DPS
−3 DN2
SP4/SP8
1.5
DPL
DPS
−0.5 −1
0.5 0 −0.5 −1 −1.5
−1
−2
−1.5
DN3
DN4
DPL
DPS
−2.5 DN2
SP4/SP8
DN3
Cluster 14
DN4
DPL
DPS
−2 DN2
SP4/SP8
2
2
1.5
1.5
−0.5 −1
0.5 0 −0.5 −1
−1.5 −2 DN2
1
DN4
DPL
DPS
−2 DN2
SP4/SP8
1 0.5 0 −0.5 −1
−1.5 DN3
Cluster 17
DN4
DPL
DPS
−2 DN2
SP4/SP8
DN4
DPL
DPS
−2.5 DN2
SP4/SP8
1.5
1.5
1.5
1
1
−2 −2.5 DN2
DN3
DN4
Figure S 1:
DPL
DPS
SP4/SP8
0 −0.5
0.5 0 −0.5
0.5 0 −0.5
−1
−1
−1
−1.5
−1.5
−1.5
−2 DN2
DN3
DN4
DPL
DPS
SP4/SP8
−2 DN2
DPL
1
Gene expression
Gene expression
−1.5
Gene expression
1.5
0.5
DN4
Cluster 20 2
−1
DN3
Cluster 19 2
−0.5
SP4/SP8
−2 DN3
Cluster 18
0
DPS
−1
2
1
SP4/SP8
0 −0.5
2
0.5
DPS
0.5
−1.5
−1.5 DN3
DPL
1
Gene expression
0
Gene expression
2.5
2 1.5
Gene expression
2.5
DN4
Cluster 16
2
0.5
DN3
Cluster 15
1.5 1
SP4/SP8
0 −0.5
−2
Cluster 13 2.5
DPS
1 0.5
−1.5
−2.5 DN2
SP4/SP8
Gene expression
Gene expression DN4
0
DPL
2.5
Gene expression
2
1
1 0.5
DN4
Cluster 12
2
DN3
DN3
Cluster 11 1.5
−2 DN2
SP4/SP8
−2
2
−1
DPS
0
1.5
−1.5
SP4/SP8
−1
2
−0.5
DPS
1
1.5
0
DPL
2
Cluster 10
0.5
DN4
3
0
−1
Cluster 9
1
DN3
Cluster 8
0.5
−1.5 −2 DN2
DN4
1
Gene expression
Gene expression
1
−0.5
−2.5 DN2
−1
Cluster 7
1.5
0.5
0 −0.5
−1.5
Cluster 6
1
Gene expression
−1
−2
Cluster 5
Gene expression
0 −0.5
0.5
Gene expression
DN4
0.5
−1.5
−1.5 DN3
1
Gene expression
0
Gene expression
Gene expression
Gene expression
0.5
−2 DN2
1
1
1
−1.5
Gene expression
Cluster 4
2
2 1.5
Gene expression
Cluster 3
2.5
DN3
DN4
DPL
DPS
SP4/SP8
−2 DN2
DN3
DN4
DPL
Clusters from MixDTrees-MAP on TCell. We depict the 20 clusters found in TCell, expression values on the y-axis, and cell types on the x-axis. Lines corresponding to developmental profile values between stages DN2, DN3, DN4, DPL, DPS and SP4 are in green and between DPS and SP8 in red.
Cluster 2 1
1.5
1
0.5
1
0.5 0 −0.5
0 −0.5 −1 −1.5
large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
2
1.5
1.5
1
Imm. B
−1.5 Pre−BI
Mat. B
−0.5
0 −0.5 −1
large Pre−BII small Pre−BII
Imm. B
−1.5 Pre−BI
Mat. B
large Pre−BII small Pre−BII
0.5 0 −0.5 −1
large Pre−BII small Pre−BII
Imm. B
−1.5 Pre−BI
Mat. B
Cluster 7
0.5
Cluster 9
Imm. B
2
2 1.5
0 −0.5 −1
−1
−1.5
−1.5 large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
Cluster 11 2
1
1.5
1
0.5
0.5
−1 −1.5 Pre−BI
−1 −1.5
large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
Cluster 13
0 −0.5 −1
Imm. B
−2 Pre−BI
Mat. B
Cluster 14
large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
Cluster 15 1
1
1
0.5
0.5
−0.5 −1 −1.5 Pre−BI
−0.5 −1
large Pre−BII small Pre−BII
Imm. B
−1.5 Pre−BI
Mat. B
Cluster 17
0 −0.5 −1 −1.5
large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
Cluster 18
0 −0.5 −1 −1.5
large Pre−BII small Pre−BII
Imm. B
−2 Pre−BI
Mat. B
Cluster 19 1
1
1
1
0.5
−0.5 −1 −1.5 Pre−BI
0.5 0 −0.5 −1
large Pre−BII small Pre−BII
Figure S 2:
Imm. B
Mat. B
−1.5 Pre−BI
1.5
Gene expression
2 1.5
Gene expression
2 1.5
Gene expression
2
0
0.5 0 −0.5 −1
large Pre−BII small Pre−BII
Imm. B
Mat. B
−1.5 Pre−BI
large Pre−BII small Pre−BII
Cluster 20
1.5
0.5
Mat. B
1.5
Gene expression
1
Gene expression
1.5
Gene expression
2
0
large Pre−BII small Pre−BII
Cluster 16
1.5
0.5
Imm. B
−1.5
2
0
Mat. B
0 −0.5
1.5
0.5
Imm. B
0.5
−1
−1.5
large Pre−BII small Pre−BII
Mat. B
1
Gene expression
−0.5
Gene expression
1.5
1
0
large Pre−BII small Pre−BII
Cluster 12
1.5
−0.5
Imm. B
0 −0.5
2
0
Mat. B
0.5
1.5
0.5
Imm. B
1
0.5
−2 Pre−BI
Mat. B
large Pre−BII small Pre−BII
Cluster 8
1.5
Cluster 10
Gene expression
Gene expression
−0.5
Gene expression
0
−1
Gene expression
0
1
1 0.5
−1.5 Pre−BI
1
0.5
Cluster 6
Gene expression
Gene expression
Cluster 5
Cluster 4 1.5
−1
large Pre−BII small Pre−BII
Gene expression
−1.5 Pre−BI
Gene expression
1.5
Gene expression
Gene expression
2
−1
Gene expression
Cluster 3
1.5
Gene expression
Cluster 1 2
0 −0.5 −1 −1.5
large Pre−BII small Pre−BII
Imm. B
Mat. B
−2 Pre−BI
large Pre−BII small Pre−BII
Imm. B
Mat. B
Clusters from MixDTrees-MAP on BCell. We depict the 20 clusters found in BCell, expression values on the y-axis, and cell types on the x-axis. Lines corresponding to developmental profile values between between all stages are in red.
Cluster 2
0.6
0.6
0.6
0 −0.2
0.4 0.2 0 −0.2
0 −0.2
−0.4
−0.4
−0.6
−0.6
−0.6
NK/SP4/pro−B
pro−B
−0.8 pHSC
immature B
NK/SP4/pro−B
pro−B
−0.8 pHSC
immature B
Cluster 6 1
0.8
0.6
0.8
0.6
0.6
0 −0.2
0.2 0 −0.2
pro−B
−0.8 pHSC
immature B
Cluster 9
NK/SP4/pro−B
pro−B
0
−0.5
pro−B
−1 pHSC
immature B
pro−B
−1 pHSC
immature B
NK/SP4/pro−B
pro−B
0.8
0.8
0.6 0.4
0.4 0.2 0
−0.6 pHSC
immature B
0.2
0 −0.2 −0.4
0
Gene expression
Gene expression
0.4 0.2
−0.2 −0.4 −0.6
−0.6
NK/SP4/pro−B
pro−B
−1 pHSC
immature B
Cluster 17
pro−B
pro−B
−1 pHSC
immature B
0.8
0.6
0.6
0.4
0.4
0.2 0 −0.2 −0.4
−1 pHSC
immature B
−0.5
Figure S 3:
immature B
−0.6 −0.8 NK/SP4/pro−B
pro−B
−1 pHSC
immature B
0.8 0.6
−0.2 −0.4
−1 pHSC
0.2 0 −0.2 −0.4
NK/SP4/pro−B
pro−B
immature B
immature B
0.2 0 −0.2 −0.4 −0.6
−0.6 −0.8 pHSC
pro−B
0.4
0.4
0
NK/SP4/pro−B
Cluster 20
0.6
−0.8 pro−B
−0.4
0.8
−0.6
NK/SP4/pro−B
0
0.6
Gene expression
Gene expression
0
immature B
−0.2
0.8
0.2
pro−B
0.2
Cluster 19
0.4
0.5
NK/SP4/pro−B
Cluster 16
0.8
Cluster 18
1
−0.4
−0.8 NK/SP4/pro−B
−0.8 NK/SP4/pro−B
0 −0.2
−0.6
−0.6 −0.8
−0.8
0.2
Cluster 15
0.4
0.6
NK/SP4/pro−B
Cluster 12
1
Cluster 14
0.8
−1 pHSC
NK/SP4/pro−B
Gene expression
NK/SP4/pro−B
immature B
0
−0.5
−0.4
Cluster 13
−1 pHSC
0
−0.2
−0.4 −0.6 pHSC
pro−B
0.5
0.6
Gene expression
Gene expression
−0.2
immature B
1
Cluster 11
0.5
0
pro−B
Cluster 8
−0.2
−0.8 pHSC
immature B
0.6
0.2
NK/SP4/pro−B
−0.6
1
0.4
−0.8 pHSC
immature B
0.2
Cluster 10
0.8
pro−B
−0.4
−0.6 NK/SP4/pro−B
0 −0.2
−0.6 NK/SP4/pro−B
Gene expression
−0.8 pHSC
0.4
−0.4
−0.6
0.2
−0.4
0.4
Gene expression
Gene expression
0.2
0.4
Cluster 7
0.8
−0.4
Gene expression
0.2
−0.4
0.4
Gene expression
0.4
Gene expression
0.2
Gene expression
0.4
Gene expression
0.6
Gene expression
1 0.8
Cluster 5
Gene expression
Cluster 4
1 0.8
−0.8 pHSC
Gene expression
Cluster 3
1 0.8
Gene expression
Gene expression
Cluster 1 1 0.8
−0.8 NK/SP4/pro−B
pro−B
immature B
−1 pHSC
NK/SP4/pro−B
pro−B
immature B
Clusters from MixDTrees-MAP on LymphoidTree. We depict the 20 clusters found in LymphoidTree, expression values on the y-axis, and cell types on the x-axis. Lines corresponding to developmental profile values between stages HSC, pro-B, pre-B and immature B Cell are in read, between HSC and Natural Killer in blue, and between HSC and SP4 in green.
100 0
BIC
−100 −200 −300 −400 −500 −600 10
15
20
25
30
Number of Clusters
Figure S 4: BIC vs number of components in the data set LympTree from MixDTrees-MAP. The minimum BIC value obtained indicates the ’optimal’ number of clusters, 20 for this data set.
microRNA enrichment in TCell 16
−log p−values MixDTrees
14
12
10
8
6
4
2 2
4
6
8
10
12
14
16
−log p−values SOM
Figure S 5: Scatter plot comparing the microRNAs enrichment of SOM (x-axis) and MixDTrees-MAP (y-axis) on TCell. For visual purposes, we use −log(p)-values, where higher values indicates a higher enrichment. The blue lines corresponds to −log(p)-value cut-off used (p-value of 0.05). Values to the left of the vertical blue line (below the horizontal blue line) indicate that no enrichment was found for MixDTrees-MAP (or SOM). We included only microRNAs with a −log(p)-value higher then (2.99) in one of the results. Points above the red line indicates a higher enrichment for MixDTrees-MAP results, and values bellow it to SOM. MixDTrees-MAP has a higher −log(p)-value in 9 out of the 14 microRNAs, while SOM has enrichment for one microRNA, which is not detected in MixDTrees-MAP.
microRNA enrichment in BCell 16
−log p−values MixDTrees
14
12
10
8
6
4
2 2
4
6
8
10
12
14
16
−log p−values SOM
Figure S 6: Scatter plot comparing the microRNA enrichment of SOM (x-axis) and MixDTrees-MAP (y-axis) on BCell. For visual purposes, we use −log(p)-values, where higher values indicates a higher enrichment. The blue lines corresponds to −log(p)-value cut-off used (p-value of 0.05). Values to the left of the vertical blue line (below the horizontal blue line) indicate that no enrichment was found for MixDTrees-MAP (or SOM). We included only microRNAs with a −log(p)-value higher then (2.99) in one of the results. Points above the red line indicate a higher enrichment for MixDTrees-MAP, and values bellow it to SOM. MixDTrees-MAP has a higher −log(p)-value in 8 out of the 14 microRNAs, and it also has enrichment in 7 microRNAs not find with SOM.
microRNA enrichment CDF in TCell 1 0.8
F(x)
0.6 0.4 0.2 0 0
SOM MixDTrees 0.02
0.04 0.06 p−value
0.08
0.1
Figure S 7: Empirical cumulative distribution function (CDF) of microRNAs enrichment of SOM (blue line) and MixDTrees-MAP (red line) on TCell. The plots shows no clear distinctions between the CDFs of the two methods.
microRNA enrichment CDF in BCell 1 0.8
F(x)
0.6 0.4 0.2
SOM MixDTrees
0 0
0.05
0.1 p−values
0.15
0.2
Figure S 8: Empirical cumulative distribution function (CDF) comparing the microRNAs enrichment of SOM (blue line) and MixDTrees-MAP (red line) on BCell. MixDTrees-MAP has clearly a p-value distribution towards lower values than SOM.
microRNA enrichment in TCell −log p−values Mixture of Trees MAP
16
14
12
10
8
6
4
2 2
4
6
8
10
12
14
16
−log p−values Mixture of Trees MLE
Figure S 9: Scatter plot comparing the microRNA enrichment of MixDTrees-MLE (x-axis) and MixDTrees-MAP (y-axis) on TCell. For visual purposes, we use −log(p)-values, where higher values indicates a higher enrichment. The blue lines corresponds to −log(p)-value cutoff used (p-value of 0.05). Values to the left of the vertical blue line (below the horizontal blue line) indicate that no enrichment was found for MixDTrees-MAP (or MixDTrees-MLE). We included only microRNAs with a −log(p)-value higher then (2.99) in one of the results. Points above the red line indicate a higher enrichment for MixDTrees-MAP, and values bellow it to MixDTrees-MLE. MixDTrees-MAP has a higher −log(p)-value in 9 out of the 14 microRNAs, and it also has enrichment in 4 microRNAs not enriched with MixDTrees-MLE.
microRNA enrichment in BCell −log p−values Mixture of Trees MAP
10
8
6
4
2 2
4
6
8
10
−log p−values Mixture of Trees MLE
Figure S 10: Scatter plot comparing the microRNA enrichment of MixDTrees-MLE (x-axis) and MixDTrees-MAP (y-axis) on BCell. For visual purposes, we use −log(p)-values, where higher values indicates a higher enrichment. The blue lines corresponds to −log(p)-value cutoff used (p-value of 0.05). Values to the left of the vertical blue line (below the horizontal blue line) indicate that no enrichment was found for MixDTrees-MAP (or MixDTrees-MLE). We included only microRNAs with a −log(p)-value higher then (2.99) in one of the results. Points above the red line indicate a higher enrichment for MixDTrees-MAP, and values bellow it to MixDTrees-MLE. MixDTrees-MAP has a higher −log(p)-value in 6 out of the 13 microRNAs, and it also has enrichment in 2 microRNAs not enriched with MixDTrees-MLE.
Cluster size Distribution BCell
Cluster size Distribution TCell
10 MixDTrees−MAP MixDTrees−MLE SOM
6 4 2 0
MixDTrees−MAP MixDTrees−MLE SOM
5 cluster size
cluster size
8
6
4 3 2 1
14 36 58 80 102 124 146 168 190 212 no. clusters
0 0
50
100 no. clusters
150
200
Figure S 11: Cluster size distributions for MixDTree-MAP, MixDTree-MLE and SOM results on BCell (left) and TCell (right). For BCell, SOM and MixDTrees-MAP have similar cluster size distribution, while MixDTrees-MLE has more clusters of small size (6 with less then 25 genes) and one with large size (more then 200 genes). For TCell, cluster size distributions do not differ, however, MixDTrees-MLE has more smaller clusters, 5 with less than 26 genes.
