mirsynergy: Detect synergistic miRNA regulatory modules by overlapping...

Description Usage Arguments Details Value Author(s) References Examples

View source: R/mirsynergy.R

Description

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.

Usage

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mirsynergy(W, H, alpha = 2, merge.tol = 0.8, 
  density1.tol = 1e-2, density2.tol=5e-3, verbose = FALSE)

Arguments

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.

Details

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.

Value

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

Author(s)

Yue Li

References

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

Examples

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##---- 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)

Example output

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

Mirsynergy documentation built on May 2, 2018, 3:27 a.m.