=Paper= {{Paper |id=Vol-3060/paper-1 |storemode=property |title=Gene Selection for Cancer Diagnosis via Iterative Graph Clustering-Based Approach Communication |pdfUrl=https://ceur-ws.org/Vol-3060/paper-1.pdf |volume=Vol-3060 |authors=Mehrdad Rostami,Mourad Oussalah |dblpUrl=https://dblp.org/rec/conf/aiia/Rostami021 }} ==Gene Selection for Cancer Diagnosis via Iterative Graph Clustering-Based Approach Communication== https://ceur-ws.org/Vol-3060/paper-1.pdf
Gene Selection for Cancer Diagnosis via Iterative
Graph Clustering-based Approach
Mehrdad Rostami1 , Mourad Oussalah1,2
1
    Centre of Machine Vision and Signal Processing, Faculty of Information Technology, University of Oulu, Oulu, Finland
2
    Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, Finland


                                         Abstract
                                         The development of microarray devices has led to the accumulation of DNA microarray datasets. Through
                                         this technological advance, physicians are able to examine various aspects of gene expression for cancer
                                         diagnosis. As data accumulation rapidly increases, the task of machine learning faces considerable
                                         challenges for high-dimensional DNA microarray data classification. Gene selection is a popular and
                                         powerful approach to deal with these high-dimensional cancer data. In this paper, a novel graph
                                         clustering-based gene selection approach is developed. The developed approach has two main objectives,
                                         consisting of relevance maximization and redundancy minimization of the selected genes. In this method,
                                         in each iteration, one subgraph is extracted, and then among the existing genes in this cluster, appropriate
                                         genes are selected using filter-based measure. The reported results on five cancer datasets indicate that
                                         the developed gene selection approach can improve the accuracy of cancer diagnosis.

                                         Keywords
                                          Cancer diagnosis, Microarray data classification, Gene selection, Feature selection, Graph clustering




1. Introduction
Worldwide, cancer remains the leading cause of death for both men and women. Cancer
diagnosis is important to increase survival chances since early treatment is available to the
patients, provided successful early diagnosis. As a result, much research has been conducted to
develop better strategies to prevent, diagnose, and treat this disease to decrease the mortality
[1, 2]. Using the emerging DNA microarray data, in an experiment, multiple aspects of gene
expression can be investigated to diagnose or detect different kinds of cancer.
Existing machine learning and pattern recognition approaches to handle large volume of DNA
microarray have been challenged by the high-dimensional structure of a such data [3]. The high
data volume makes many genes irrelevant or redundant to cancer diagnosis or classification
task. Gene selection is a powerful and efficient technique in microarray data to deal with this
challenge [3]. By using this strategy, the training process can be simplified, which, in turn,
enhances machine learning performance, and, thereby, the general diagnosis [4].
The main goal of our study is to develop an efficient clustering-based approach to choose a
subset of primary genes where one cluster of genes is chosen at each iteration. Then, among
the existing genes in this cluster, appropriate ones are selected using a filter-based measure.
AIxIA 2021 SMARTERCARE Workshop, November 29, 2021, Milan, IT
Envelope-Open Mehrdad.Rostami@oulu.fi (M. Rostami); Mourad.Oussalah@oulu.fi (M. Oussalah)
Orcid 0000-0001-5710-217X (M. Rostami); 0000-0002-4422-8723 (M. Oussalah)
                                       © 2021 Copyright for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).
    CEUR
    Workshop
    Proceedings
                  http://ceur-ws.org
                  ISSN 1613-0073
                                       CEUR Workshop Proceedings (CEUR-WS.org)



                                                                                                           1
Mehrdad Rostami et al. CEUR Workshop Proceedings                                                1–6


This process of finding a cluster and selecting a candidate gene from each cluster is iterated
until all clusters are selected. We expect that our model, in addition to selecting genes with the
least amount of redundancy, will also maximize the relevancy of selected genes.
The remainder of this paper is organized as below: Section 2 reviews some related works. The
developed prediction method is presented in Section 3. The experimental results are reported
in section 4 and finally, section 5 present the conclusion and future works.


2. Related Works
A significant challenge in handling microarray data for cancer diagnosis is their high-dimensionality
where the number of genes is much greater than the number of patterns [5, 6, 7], which leads
to a well-known problem known as “curse of dimensionality”. Gene selection is one popu-
lar technique to eliminate irrelevant and/or redundant genes [8]. Previously, gene selection
approaches were classified as filter, wrapper, hybrid, and embedded approaches. In the filter
techniques, relevant genes are evaluated without a learning model. As a result, these techniques
are typically fast [9]. There have been many filter-based approaches for gene selection in cancer
diagnosis such as, Filtering and ranking techniques [10], Simplified Swarm Optimization (SSO)
[11], Tabu Asexual Genetic Algorithm (TAGA) [12], Feature Clustering and Feature Discretiza-
tion assisting gene selection (FCFD) [13], Least Loss (LL) [14], etc. The wrapper gene selection
strategies employ a learning model to evaluate the efficiency of the chosen gene subset [15].
In this category, an iterative search algorithm-based process is applied to seek the optimum
gene subset, and at each step, a subset of original genes are chosen and with a fitness function
determining which genes are the best. Despite the fact that wrapper strategies choose a effective
subset of original genes, they are computationally complex and may present challenges within
analysis of DNA microarray datasets [16]. Hybrid strategies combine the benefits of both filter
and wrapper strategies [16]. In addition, the embedded strategies make use of gene selection in
the learning process.


3. Proposed Method
Our novel gene selection algorithm is introduced by combining the notions of Graph Clustering
with Feature Weighting (GCFW). We can group our algorithm under the category of filter
gene selection technique and this algorithm measure relevancy and redundancy notions in
its selection mechanism. GCFW consists of two main phases including (1) Gene similarity
calculation, (2) Iterative subgraph finding and gene selection. In the reminder of this section
the details of these two phases are explained.

3.1. Gene similarity calculation
Initially, microarray datasets are represented as a weighted graph. In this demonstration, each
gene is indicated by a node and the value of each edge shows by gene similarities. In this graph
representation, the Pearson correlation coefficient criterion [17] is used to measure the similarity
values between two genes. This similarity measure maps the gene space of a microarray dataset



                                                 2
Mehrdad Rostami et al. CEUR Workshop Proceedings                                                    1–6


into a fully weighted and connected graph. To make the graph sparser, the edges with values
lower than the threshold 𝜃 are deleted. 𝜃 is an adjustable parameter and takes its value in the
range [0 1]. In our experiment 𝜃 is set to 0.6.

3.2. Iterative subgraph finding and gene selection
In order to avoid choosing similar genes, initial genes are divided to several groups to to reduce
the possibility of selecting redundant genes. Moreover to select a subset of relevant genes, a
feature weighting strategy is developed. In the proposed method, in each iteration, a subgraph
is identified and then among these present genes in this subgraph, the suitable ones are chosen
using gene relevance.
The purpose of the subgraph discovery is to divide the genes into clusters so that the genes of
each cluster are as similar as possible. Previous gene clustering algorithms suffer from inherent
shortcomings, like the need to specify the number of clusters, ignoring the distribution of genes
and equal consideration of all genes. To deal with these issues, quite different from existing
feature clustering algorithms, a fast algorithm for subgraph discovery [18] is employed for gene
clustering. This algorithm yields grouping faster than previous gene clustering method.
Moreover, in this proposed method, Fisher Score weighting technique is used to rank the
genes of each subgraph and select the relevant genes for representing the genes of that cluster.
Therefore, it can claim that the genes selected satisfy both qualities: maximum relevancy and
minimal redundancy. In other words, the use of subgraph discovery criteria avoids to choose
the redundant genes and utilization of the notion of feature weighting results in the selection of
appropriate genes.Then, from each subgraph, the relevant gene is selected by performing the
feature weighting technique. The purpose of feature weighting is to select a representative gene
that is most relevant to the cancer diagnosis task. Fisher Score (FS) is a supervised univariate
filter which gives higher values to those genes that have a separation property. The Fisher Score
of gene k is calculated as below:
                                                                       2
                                                 ∑𝑣∈𝑉 𝑛𝑣 (𝐺𝑘𝑣̄ − 𝐺𝑘̄ )
                                   𝐹 𝑆 (𝐺𝑘 ) =                                                       (1)
                                                     𝑛𝑣 (𝜎𝑣 (𝐺𝑘 ))2

where 𝐺𝑘̄ is the average value of all the patterns related to the gene 𝐺𝑘 , 𝑉 is a set of all classes in
a dataset, 𝑛𝑣 is the size of samples on the class v, and 𝜎𝑣 (𝐺𝑘 ) and 𝐺𝑘𝑣̄ indicates the variance and
mean of gene 𝐺𝑘 on class v, respectively.
According to the algorithm design, a subgraph of genes is extracted in each iteration using a
repetitive process, and then the appropriate genes are selected from the existing genes in this
subgraph using a feature-weighting strategy. This process is repeated again for all remaining
genes after deleting the genes present in the extracted subgraph.


4. Experimental results
To investigate the performance of our cancer diagnosis algorithm, various experiments are
performed.The efficiency of our algorithm is compared with three new methods of filter-based




                                                     3
Mehrdad Rostami et al. CEUR Workshop Proceedings                                               1–6


Table 1
Characteristics of the used microarray datasets
                         Dataset           # Genes     # Classes   # Patterns
                         Colon             2000        2           62
                         SRBCT             2328        4           83
                         Leukemia          7129        2           72
                         Prostate Tumor    10509       2           102
                         Lung Cancer       12600       5           203




Figure 1: Average accuracy of different methods on (a) SVM classifiers (b) AB classifiers.


cancer diagnosis: Tabu Asexual Genetic Algorithm (TAGA) [12], Feature Clustering and Fea-
ture Discretization assisting gene selection (FCFD) [13], Least Loss (LL) [14]. Moreover, the
experiments in this study use a variety of datasets with different properties to demonstrate the
effectiveness of the developed algorithm. These microarray data include of Colon, Leukemia,
SRBCT, Prostate Tumor, and Lung Cancer [6]. The primary characteristics of these datasets are
detailed in Table 1. Additionally, to assess the flexibility of the proposed algorithm on different
classifiers, we also examined the performance of two frequent used classifiers, including Support
Vector Machine (SVM) and AdaBoost (AB).
   In our experiments, the efficiency of our algorithm is measured using the mentioned classifiers.
Figure 1 summarizes the average classification accuracy over ten separate and autonomous
runs of the different gene selection algorithms. The reported results indicate that in all cancer
datasets, the developed gene selection performs better than those of other alternative approaches.
For example, for the Colon dataset on SVM classifier, the proposed algorithm obtained a 88.91%
accuracy while for TAGA [12], FCFD [13], LL [14], this value is 81.52%, 87.82% and 87.24%, cor-
respondingly. Furthermore, the reported results for AB classifier were similar to SVM classifier,
and in all cases the developed algorithm was more precise than the other compared algorithms.




                                                  4
Mehrdad Rostami et al. CEUR Workshop Proceedings                                                1–6


5. Conclusion
In this paper, an efficient dimensionality reduction algorithm in cancer diagnosis has been de-
veloped utilizing the subgraph discovery and feature weighting. The main aim of our algorithm
is to choose a subset of appropriate and non-redundant genes that are most closely associated
to the target class of microarray data classification. The proposed algorithm has been compared
to the recent gene selection algorithms on the cancer microarray datasets. The experimental
results show that our cancer diagnosis algorithm gained the highest performance.
In future work, our goals are (1) integrate our proposed gene selection approach along with deep
learning techniques for accurate cancer diagnosis, and (2) study explainable artificial intelligence
in detail to see how explainable artificial intelligence can improve further interpretability and
transparency of diagnosis.


Acknowledgments
This project is supported by the Academy of Finland Profi5 DigiHealth project, which is gratefully
acknowledged.


References
 [1] S. Yang, H. Xiao, L. Cao, Recent advances in heat shock proteins in cancer diagnosis,
     prognosis, metabolism and treatment, Biomedicine & Pharmacotherapy 142 (2021) 112074.
 [2] R. Daneshjou, B. He, D. Ouyang, J. Y. Zou, How to evaluate deep learning for cancer
     diagnostics – factors and recommendations, Biochimica et Biophysica Acta (BBA) - Reviews
     on Cancer 1875 (2021) 188515. doi:https://doi.org/10.1016/j.bbcan.2021.188515 .
 [3] Y. Liu, F. Nie, Q. Gao, X. Gao, J. Han, L. Shao, Flexible unsupervised feature extraction for
     image classification, Neural Networks 115 (2019) 65–71. doi:https://doi.org/10.1016/
     j.neunet.2019.03.008 .
 [4] S. Forouzandeh, K. Berahmand, M. Rostami, Presentation of a recommender system
     with ensemble learning and graph embedding: a case on movielens, Multimedia Tools
     and Applications 80 (2021) 7805–7832. URL: https://doi.org/10.1007/s11042-020-09949-5.
     doi:10.1007/s11042- 020- 09949- 5 .
 [5] M. Rostami, K. Berahmand, E. Nasiri, S. Forouzandeh, Review of swarm intelligence-
     based feature selection methods, Engineering Applications of Artificial Intelligence 100
     (2021) 104210. URL: https://www.sciencedirect.com/science/article/pii/S0952197621000579.
     doi:https://doi.org/10.1016/j.engappai.2021.104210 .
 [6] M. Rostami, S. Forouzandeh, K. Berahmand, M. Soltani, Integration of multi-objective
     pso based feature selection and node centrality for medical datasets, Genomics 112 (2020)
     4370–4384. URL: https://www.sciencedirect.com/science/article/pii/S088875432030224X.
     doi:https://doi.org/10.1016/j.ygeno.2020.07.027 .
 [7] M. Rostami, K. Berahmand, S. Forouzandeh, A novel method of constrained feature selec-
     tion by the measurement of pairwise constraints uncertainty, Journal of Big Data 7 (2020)
     83. URL: https://doi.org/10.1186/s40537-020-00352-3. doi:10.1186/s40537- 020- 00352- 3 .



                                                 5
Mehrdad Rostami et al. CEUR Workshop Proceedings                                               1–6


 [8] M. Rostami, K. Berahmand, S. Forouzandeh, A novel community detection based genetic
     algorithm for feature selection, Journal of Big Data 8 (2021) 2. URL: https://doi.org/10.
     1186/s40537-020-00398-3. doi:10.1186/s40537- 020- 00398- 3 .
 [9] M. Labani, P. Moradi, F. Ahmadizar, M. Jalili, A novel multivariate filter method for
     feature selection in text classification problems, Engineering Applications of Artifi-
     cial Intelligence 70 (2018) 25–37. URL: https://www.sciencedirect.com/science/article/
     pii/S0952197617303172. doi:https://doi.org/10.1016/j.engappai.2017.12.014 .
[10] W. De Smet, K. De Loof, P. De Vos, P. Dawyndt, B. De Baets, Filtering and ranking
     techniques for automated selection of high-quality 16s rrna gene sequences, Systematic
     and Applied Microbiology 36 (2013) 549–559. URL: https://www.sciencedirect.com/science/
     article/pii/S0723202013001495. doi:https://doi.org/10.1016/j.syapm.2013.09.001 .
[11] C.-M. Lai, H.-P. Huang, A gene selection algorithm using simplified swarm optimization
     with multi-filter ensemble technique, Applied Soft Computing 100 (2021) 106994. URL:
     https://www.sciencedirect.com/science/article/pii/S1568494620309339. doi:https://doi.
     org/10.1016/j.asoc.2020.106994 .
[12] S. Salesi, G. Cosma, M. Mavrovouniotis, Taga: Tabu asexual genetic algorithm em-
     bedded in a filter/filter feature selection approach for high-dimensional data, Informa-
     tion Sciences 565 (2021) 105–127. URL: https://www.sciencedirect.com/science/article/pii/
     S0020025521000475. doi:https://doi.org/10.1016/j.ins.2021.01.020 .
[13] H.-Y. Lin, Feature clustering and feature discretization assisting gene selection for molecular
     classification using fuzzy c-means and expectation–maximization algorithm, The Journal
     of Supercomputing 77 (2021) 5381–5397. URL: https://doi.org/10.1007/s11227-020-03480-y.
     doi:10.1007/s11227- 020- 03480- y .
[14] F. Thabtah, F. Kamalov, S. Hammoud, S. R. Shahamiri, Least loss: A simplified fil-
     ter method for feature selection, Information Sciences 534 (2020) 1–15. URL: https:
     //www.sciencedirect.com/science/article/pii/S0020025520304242. doi:https://doi.org/
     10.1016/j.ins.2020.05.017 .
[15] M. Rostami, P. Moradi, A clustering based genetic algorithm for feature selection, in:
     2014 6th Conference on Information and Knowledge Technology (IKT), 2014, pp. 112–116.
     doi:10.1109/IKT.2014.7030343 .
[16] P. García-Díaz, I. Sánchez-Berriel, J. A. Martínez-Rojas, A. M. Diez-Pascual, Unsupervised
     feature selection algorithm for multiclass cancer classification of gene expression rna-seq
     data, Genomics 112 (2020) 1916–1925. URL: https://www.sciencedirect.com/science/article/
     pii/S0888754319304811. doi:https://doi.org/10.1016/j.ygeno.2019.11.004 .
[17] M. M. Kabir, M. Shahjahan, K. Murase, A new local search based hybrid genetic
     algorithm for feature selection, Neurocomputing 74 (2011) 2914–2928. URL: https:
     //www.sciencedirect.com/science/article/pii/S0925231211002748. doi:https://doi.org/
     10.1016/j.neucom.2011.03.034 .
[18] M. Bressan, Faster algorithms for counting subgraphs in sparse graphs, Algorith-
     mica 83 (2021) 2578–2605. URL: https://doi.org/10.1007/s00453-021-00811-0. doi:10.1007/
     s00453- 021- 00811- 0 .




                                                 6