Description Usage Arguments Details Value Author(s) References Examples
Detect synergistic miRNA regulatory modules by overlapping neighbourhood expansion using a deterministic overlapping clustering algorithm adapted from a recently developed framework. Mirsynergy operates in two stages that first forms MRM based on co-occurring miRNAs and then expand the MRM by greedily including (excluding) mRNA into (from) the MRM to maximize the synergy score, which is a function of miRNA-mRNA and gene-gene interactions.
1 2 | mirsynergy(W, H, alpha = 2, merge.tol = 0.8,
density1.tol = 1e-2, density2.tol=5e-3, verbose = FALSE)
|
W |
An N by M edge weight matrix containing interaction strength between N mRNA and M miRNA. |
H |
An N by N edge weight matrix containing the binary interaction among the N mRNA (genes). |
alpha |
Penalty for including a node into the growing module (advanced option). See manuscript or Nepusz et al. (2012) for more details. |
merge.tol |
Threshold with range [0,1] to merge modules based on the percentage of nodes shared between the two modules. |
density1.tol |
Threshold with range [0,1] to filter modules by the density function at stage 1 clustering. |
density2.tol |
Threshold with range [0,1] to filter modules by the density function 2 at stage 2 clustering. |
verbose |
Binary indicator to show running info. |
The weight matrix W can be obtained by various approaches such as Pearson correlation or linear regression on mRNA and miNRA expression profiles across multiple samples. Matrix H can be obtained from public database such as TRANSFAC and BioGrid.
A nested list containing each item as a miRNA regulatory module (MRM). Each item itself is a list containing the following information:
miRNA |
miRNA included in the MRM |
mRNA |
mRNA included in the MRM |
v.in |
miRNA and mRNA |
v.bound |
miRNA and mRNA disregard or excluded from the MRM but still have nonzero connection with the internal nodes |
card.m |
Number of miRNA in the MRM |
card.t |
Number of mRNA targets in the MRM |
card |
Total number of miRNA and mRNA targets in the MRM |
density |
Density of the MRM |
Yue Li
Nepusz, T., Yu, H., & Paccanaro, A. (2012). Detecting overlapping protein complexes in protein-protein interaction networks. Nature Methods, 9(5), 471-472. doi:10.1038/nmeth.1938
1 2 3 4 5 6 7 8 9 10 11 | ##---- Should be DIRECTLY executable !! ----
##-- ==> Define data, use random,
##-- or do help(data=index) for the standard data sets.
##
# simulate N mRNA and M miRNA and their interaction matrices
load(system.file("extdata/toy_modules.RData", package="Mirsynergy"))
# run mirsynergy clustering
V <- mirsynergy(W, H, verbose=TRUE)
summary_modules(V)
|
Loading required package: igraph
Attaching package: 'igraph'
The following objects are masked from 'package:stats':
decompose, spectrum
The following object is masked from 'package:base':
union
Loading required package: ggplot2
Discard row/column of all zeros in W
*Stage I. Cluster 18 miRNA:
Forming new module with seed: miRNA6
add: miRNA18; w.in: 0.655; w.bound: 1.535; new synergy: 0.106
add: miRNA8; w.in: 1.152; w.bound: 1.460; new synergy: 0.134
add: miRNA12; w.in: 2.072; w.bound: 0.540; new synergy: 0.195
Forming new module with seed: miRNA3
add: miRNA9; w.in: 0.735; w.bound: 0.484; new synergy: 0.141
Forming new module with seed: miRNA17
add: miRNA2; w.in: 0.345; w.bound: 1.131; new synergy: 0.063
add: miRNA6; w.in: 0.659; w.bound: 2.466; new synergy: 0.072
add: miRNA18; w.in: 1.540; w.bound: 1.584; new synergy: 0.138
add: miRNA8; w.in: 2.037; w.bound: 1.510; new synergy: 0.150
add: miRNA12; w.in: 2.957; w.bound: 0.590; new synergy: 0.190
remove: miRNA17; w.in: 2.538; w.bound: 0.511; new synergy: 0.195
remove: miRNA2; w.in: 2.072; w.bound: 0.540; new synergy: 0.195
Forming new module with seed: miRNA2
add: miRNA17; w.in: 0.345; w.bound: 1.131; new synergy: 0.063
add: miRNA6; w.in: 0.659; w.bound: 2.466; new synergy: 0.072
add: miRNA18; w.in: 1.540; w.bound: 1.584; new synergy: 0.138
add: miRNA8; w.in: 2.037; w.bound: 1.510; new synergy: 0.150
add: miRNA12; w.in: 2.957; w.bound: 0.590; new synergy: 0.190
remove: miRNA17; w.in: 2.538; w.bound: 0.511; new synergy: 0.195
remove: miRNA2; w.in: 2.072; w.bound: 0.540; new synergy: 0.195
Forming new module with seed: miRNA10
add: miRNA15; w.in: 0.304; w.bound: 0.532; new synergy: 0.063
add: miRNA14; w.in: 0.573; w.bound: 0.649; new synergy: 0.079
add: miRNA17; w.in: 0.796; w.bound: 1.120; new synergy: 0.080
add: miRNA2; w.in: 1.233; w.bound: 1.149; new synergy: 0.100
Forming new module with seed: miRNA16
add: miRNA20; w.in: 0.219; w.bound: 0.218; new synergy: 0.049
add: miRNA17; w.in: 0.373; w.bound: 0.827; new synergy: 0.052
add: miRNA2; w.in: 0.718; w.bound: 1.041; new synergy: 0.074
add: miRNA6; w.in: 1.032; w.bound: 2.376; new synergy: 0.077
add: miRNA18; w.in: 1.913; w.bound: 1.495; new synergy: 0.124
add: miRNA8; w.in: 2.410; w.bound: 1.420; new synergy: 0.135
add: miRNA12; w.in: 3.330; w.bound: 0.500; new synergy: 0.168
Forming new module with seed: miRNA1
add: miRNA19; w.in: 0.375; w.bound: 0.000; new synergy: 0.086
Forming new module with seed: miRNA7
add: miRNA15; w.in: 0.084; w.bound: 0.383; new synergy: 0.019
add: miRNA10; w.in: 0.453; w.bound: 0.398; new synergy: 0.066
add: miRNA14; w.in: 0.736; w.bound: 0.486; new synergy: 0.080
add: miRNA17; w.in: 0.959; w.bound: 0.957; new synergy: 0.080
add: miRNA2; w.in: 1.396; w.bound: 0.986; new synergy: 0.097
Forming new module with seed: miRNA11
add: miRNA3; w.in: 0.122; w.bound: 1.015; new synergy: 0.024
add: miRNA9; w.in: 0.863; w.bound: 0.356; new synergy: 0.120
Forming new module with seed: miRNA5
MRM before merging:
M1 (synergy=0.195232383222109):
miRNA6 miRNA8 miRNA12 miRNA18
M2 (synergy=0.14089190465843):
miRNA3 miRNA9
M3 (synergy=0.195232383222109):
miRNA6 miRNA8 miRNA12 miRNA18
M4 (synergy=0.195232383222109):
miRNA6 miRNA8 miRNA12 miRNA18
M5 (synergy=0.0995481886856942):
miRNA2 miRNA10 miRNA14 miRNA15 miRNA17
M6 (synergy=0.167919254849307):
miRNA2 miRNA6 miRNA8 miRNA12 miRNA16 miRNA17 miRNA18 miRNA20
M7 (synergy=0.0857963527273969):
miRNA1 miRNA19
M8 (synergy=0.0970569736542555):
miRNA2 miRNA7 miRNA10 miRNA14 miRNA15 miRNA17
M9 (synergy=0.119598648023761):
miRNA3 miRNA9 miRNA11
M10 (synergy=0):
miRNA5
Merge cluster threshold: overlap >= 0.80:
MRM after merging/filtering:
M1 (density=3.45e-01; synergy=1.95e-01):
miRNA6 miRNA8 miRNA12 miRNA18
M2 (density=7.35e-01; synergy=1.41e-01):
miRNA3 miRNA9
M3 (density=9.31e-02; synergy=9.71e-02):
miRNA2 miRNA7 miRNA10 miRNA14 miRNA15 miRNA17
M4 (density=1.19e-01; synergy=1.68e-01):
miRNA2 miRNA6 miRNA8 miRNA12 miRNA16 miRNA17 miRNA18 miRNA20
M5 (density=3.75e-01; synergy=8.58e-02):
miRNA1 miRNA19
M6 (density=2.88e-01; synergy=1.2e-01):
miRNA3 miRNA9 miRNA11
Time elapsed for Stage I: 0.223
*Stage II. Grow MRM with mRNA:
Forming new module with seed: miRNA3,miRNA9
Forming new module with seed: miRNA6,miRNA8,miRNA12,miRNA18
add: mRNA12; w.in: 1.013; w.bound: 1.330; new synergy: 0.121
add: mRNA1; w.in: 1.926; w.bound: 1.715; new synergy: 0.165
add: mRNA9; w.in: 1.225; w.bound: 1.604; new synergy: 0.095
add: mRNA16; w.in: 2.219; w.bound: 2.509; new synergy: 0.133
Forming new module with seed: miRNA2,miRNA6,miRNA8,miRNA12,miRNA16,miRNA17,miRNA18,miRNA20
add: mRNA2; w.in: 3.191; w.bound: 2.584; new synergy: 0.161
add: mRNA9; w.in: 1.429; w.bound: 4.699; new synergy: 0.059
add: mRNA20; w.in: 3.895; w.bound: 3.289; new synergy: 0.168
Forming new module with seed: miRNA2,miRNA7,miRNA10,miRNA14,miRNA15,miRNA17
add: mRNA16; w.in: 2.423; w.bound: 5.604; new synergy: 0.086
add: mRNA2; w.in: 1.047; w.bound: 4.678; new synergy: 0.053
add: mRNA2; w.in: 4.299; w.bound: 3.872; new synergy: 0.142
add: mRNA16; w.in: 2.020; w.bound: 5.626; new synergy: 0.085
add: mRNA14; w.in: 4.984; w.bound: 3.470; new synergy: 0.154
add: mRNA10; w.in: 2.900; w.bound: 5.695; new synergy: 0.109
add: mRNA17; w.in: 3.766; w.bound: 5.134; new synergy: 0.130
add: mRNA1; w.in: 5.747; w.bound: 4.154; new synergy: 0.160
add: mRNA20; w.in: 6.985; w.bound: 3.791; new synergy: 0.180
add: mRNA13; w.in: 4.519; w.bound: 4.381; new synergy: 0.146
add: mRNA12; w.in: 7.650; w.bound: 4.341; new synergy: 0.182
add: mRNA6; w.in: 5.207; w.bound: 3.693; new synergy: 0.158
Forming new module with seed: miRNA3,miRNA9,miRNA11
add: mRNA20; w.in: 5.911; w.bound: 4.398; new synergy: 0.163
add: mRNA12; w.in: 1.013; w.bound: 2.104; new synergy: 0.091
add: mRNA1; w.in: 7.038; w.bound: 4.354; new synergy: 0.179
add: mRNA1; w.in: 1.926; w.bound: 2.488; new synergy: 0.134
add: mRNA12; w.in: 7.905; w.bound: 4.499; new synergy: 0.186
add: mRNA19; w.in: 2.584; w.bound: 2.331; new synergy: 0.153
add: mRNA8; w.in: 3.060; w.bound: 2.037; new synergy: 0.160
add: mRNA15; w.in: 8.304; w.bound: 4.101; new synergy: 0.187
Forming new module with seed: miRNA1,miRNA19
add: mRNA20; w.in: 0.861; w.bound: 1.365; new synergy: 0.105
add: mRNA16; w.in: 1.565; w.bound: 2.850; new synergy: 0.126
add: mRNA2; w.in: 2.537; w.bound: 2.925; new synergy: 0.164
Final MRM:
M1 (density=4.43e-02; synergy=1.68e-01):
miRNA6 miRNA8 miRNA12 miRNA18
mRNA2 mRNA9 mRNA16 mRNA20
M2 (density=9.63e-02; synergy=1.65e-01):
miRNA3 miRNA9
mRNA1 mRNA12
M3 (density=2.47e-02; synergy=1.87e-01):
miRNA2 miRNA7 miRNA10 miRNA14 miRNA15 miRNA17
mRNA1 mRNA2 mRNA6 mRNA10 mRNA12 mRNA13 mRNA15 mRNA16 mRNA17 mRNA20
M4 (density=2.32e-02; synergy=1.82e-01):
miRNA2 miRNA6 miRNA8 miRNA12 miRNA16 miRNA17 miRNA18 miRNA20
mRNA1 mRNA2 mRNA9 mRNA12 mRNA14 mRNA16 mRNA20
M5 (density=8.46e-02; synergy=1.64e-01):
miRNA1 miRNA19
mRNA2 mRNA16 mRNA20
M6 (density=4.86e-02; synergy=1.6e-01):
miRNA3 miRNA9 miRNA11
mRNA1 mRNA8 mRNA12 mRNA19
Total time elapsed: 0.500 (sec)
$moduleSummaryInfo
miRNA mRNA total synergy density
1 4 4 12 0.1680051 0.04426190
2 2 2 6 0.1654560 0.09630038
3 6 10 22 0.1870070 0.02471431
4 8 7 23 0.1821842 0.02318249
5 2 3 7 0.1640842 0.08457176
6 3 4 10 0.1602223 0.04856618
$miRNA.internal
modules miRNA
1 2 2
2 1 3
3 1 4
4 1 6
5 1 8
$mRNA.internal
modules mRNA
1 1 2
2 1 3
3 2 4
4 1 7
5 1 10
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