NCIS vs NetBC vs WSNF

NCIS (Liu et al., 2014) NetBC (Yu et al., 2017) WSNF (Xu et al., 2016)
Problem Cannot add a network based distance in the distance metric defined cannot discover the patterns that similar genes exhibit Identifying cancer subtypes is a crucial task for
for patients. similar behaviors only over a subset of conditions (or selecting the right treatment
samples), or relevant samples exhibit similar expression
No network structure linking all the patients (like the phenotype profiles over a subset of genes analysing the different types of data separately may
similarity network). lose the complementary information in the data of the
same patients,
Clusters may be misleading, since neighbouring genes can have
entirely different expression patterns. lack of methods utilising biological information from
networks to identify cancer subtypes.

Objective/ Goal NCIS combines gene network information to simultaneously group NetBC assigns weights to genes based on the structure identify cancer subtypes by making use of both the
samples and genes into biologically meaningful clusters. of gene interaction network, and it iteratively optimizes expression data and network information of miRNAs,
sum-squared residue to obtain the row and column TFs and mRNAs
indicative matrices of bi-clusters by matrix factorization.
Method/ Algorithm NCIS: NetBC: WSNF:
1. Assigning weights to genes (each genes) 1. assigns weights to genes based on the structure 1. Constructing the miRNA-TF-mRNA regulatory
2. Optimization: prioritize genes with large weights of gene interaction network, network
3. Co-cluster gene subtypes 2. Iteratively optimizes sum-squared residue 2. Calculating feature weight
3. obtain the row and column indicative matrices of 3. Weighted similarity network fusion
bi-clusters by matrix factorization.
Gene weights PageRank algorithm GeneRank algorithm Google PageRank algorithm
median absolute deviation (MAD) sum-squared residue median absolute deviation (MAD)
Data BRCA, GBM Lung cancer, Breast cancer BRCA, GBM
Results The main difference between them is that the objective
function of NetBC is to minimize the sum-squared
residue, while NCIS is to minimize the sum-squared
distance between entries and centroids of bi-clusters.
NCIS can only discover bi-cluster with constant values,
NetBC can not only discover bi-clusters with constant
values but also bi-clusters with coherent trend values.
Advantages The advantage of NCIS is the incorporation of the network and integrating gene interaction networks with gene miRNA-TF-mRNA regulatory network helps improve
assigning an “importance indicator” to each gene. Therefore, in expression profiles can generally boost the performance the identification of the subtypes
addition to generating the subtypes, we also obtained a bi-product – of bi-clustering in discovering cancer subtypes
the gene weights, which describe the genes’ roles in the network
and their abilities to distinguish the patient samples

NetBC assigns weights to genes by using both the gene expression profiles and gene interaction network. Genes, who regulate more genes in the gene interaction network and show larger expression variations
across samples than other genes, are viewed more important to identify cancer subtypes, and will be given larger weights
To integrate the feature variation with feature ranking, NCIS follows the idea of GeneRank to simply replace the part [(1-d)/N] in Google PageRank algorithm with the MAD to obtain the final weight of a feature.
However, we find that the final weight obtained in this way by both GeneRank and NCIS is strongly correlated with the feature weight directly calculated with Eq 2, i.e. without using MAD.

LIU, Y., GU, Q., HOU, J., HAN, J. & MA, J. 2014. A network-assisted co-clustering algorithm to discover cancer subtypes based on gene expression. BMC Bioinformatics, 15,
37.
XU, T., LE, T. D., LIU, L., WANG, R., SUN, B. & LI, J. 2016. Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data. PLOS ONE, 11,
e0152792.
YU, G., YU, X. & WANG, J. 2017. Network-aided Bi-Clustering for discovering cancer subtypes. Scientific Reports, 7, 1046.