Progress in Biophysics and Molecular Biology 177 (2023) 1–13

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Progress in Biophysics and Molecular Biology

journal homepage: www.elsevier.com/locate/pbiomolbio

A survey on gene expression data analysis using deep learning methods for
cancer diagnosis
Ravindran Ua, Gunavathi Cb, *
a
School of Information Technology and Engineering, Vellore Institute of Technology, Vellore, India
b
School of Computer Science and Engineering, Vellore Institute of Technology, Vellore, India

A R T I C L E I N F O A B S T R A C T

Keywords: Gene Expression Data is the biological data to extract meaningful hidden information from the gene dataset. This
Gene expression data gene information is used for disease diagnosis especially in cancer treatment based on the variations in gene
Data augmentation expression levels. DNA microarray is an efficient method for gene expression classification and prediction of
Deep learning methods
cancer disease for specific types of cancer. Due to the abundance of computing power, deep learning (DL) has
become a widespread technique in the healthcare sector. The gene expression dataset has a limited number of
samples but a large number of features. Data augmentation is needed for gene expression datasets to overcome
the dimensionality problem in gene data. It is a technique to generating the synthetic samples to increase the
diversity of data. Deep learning methods are designed to learn and extract the features that come from the raw
input data in the form of multidimensional arrays. This paper reviews the existing research in deep learning
techniques like Feed Forward Neural Network (FFN), Convolutional Neural Network (CNN), Autoencoder (AE)
and Recurrent Neural Network (RNN) for the classification and prediction of cancer disease and its types through
gene expression data analysis.

1. Introduction
Bioinformatics is an interdisciplinary platform for solving problems
in healthcare domain using biological data by applying computational
techniques (Yoo et al., 2012). The most popular biological data in the
healthcare domain is genomics data. Gene expression data comes from a
part of the chromosome in a human cell. There are three stages involved
in expressing the gene information. The first stage is the isolation phase,
in which messenger ribonucleic acid (mRNA) is isolated from the human
cell. The second stage is the reverse transcription phase, in which mRNA
has to perform reverse transcription-polymerase chain reaction
(RT-PCR) to get complementary deoxyribonucleic acid (cDNA) frag­
ments. The third stage is the hybridization phase, in which cDNA is
labeled with fluorescent tags and introduces the arrays with hybridiza­
tion with probes to express the gene information (https://www.your­
genome.org/facts/what-is-gene-expression.). The gene expression level
can be measured using two different technologies: RNA Sequencing
(RNA-seq) and Microarray/DNA Chip (https://sapac.illumina.com/s­
cience/technology/next-gener­
ation-sequencing/microarray-rna-seq-comparison.html?langsel = /in/.)
(https://www.youtube.com/watch?v = 2c3t3tDEmsU.). RNA-seq is a
sequencing technique that allows for the analysis of transcriptomes and
the detection of splice variants and novel sequences (Mantione et al.,
2014). Microarray technology is a technique that allows the monitoring
of thousands of gene expression levels simultaneously. Gene expression
data is mostly used for cancer classification for better prediction accu­
racy (Peng et al., 2003) (Simon, 2009).
Cancer is one of the leading causes of death worldwide, and roughly
10 million cancer deaths occurred in 2020. In general, one out of every
six deaths in the world are due to Cancer (Sung et al., 2021). Omics data
analysis is used to identify the relationships between the biological
molecules involved in a human organism. The aim of investigating omics
datasets based on genome analysis is to classify tumor and non-tumor
samples and to segregate the types of cancer (Kristensen et al., 2014).
Analyzing the genomics data is a challenging task because the dataset
consists of a limited number of samples and the number of features in the
dataset is large (Kong and Yu, 2018). Therefore, data augmentation is
often employed to increase the training sample size and to minimize
overfitting. An effective method is needed for handling the omics dataset
to overcome problems like non-reproducible results, overfitting, and
noisy data. To handle the data dimensionality problem in the dataset for
getting useful information, two methods are applied: feature selection

* Corresponding author.
E-mail address: gunavathi.cm@vit.ac.in (C. Gunavathi).

https://doi.org/10.1016/j.pbiomolbio.2022.08.004
Received 27 May 2022; Received in revised form 9 August 2022; Accepted 12 August 2022
Available online 19 August 2022
0079-6107/© 2022 Elsevier Ltd. All rights reserved.
U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

Fig. 2. Architecture of CNN.

Fig. 1. Architecture of FFN.

and feature extraction. The goal of the two techniques is to increase the
accuracy of classification and reduce the computational cost. In feature
selection, the basic principle is to select the important features from the
original datasets based on some criteria. It is a preprocessing method to
reduce redundant and irrelevant features from the dataset (Shukla et al.,
2018) (Shi et al., 2018). In feature extraction, the basic principle is to
generate the new features from the existing datasets based on some
criteria. It is a preprocessing method in which the low dimension of new
feature space is extracted from existing feature space. Some of the
feature extraction approaches are Linear Discriminant Analysis (LDA),
Principal Component Analysis (PCA), Canonical Correlation Analysis
(CCA) and Autoencoder (Tan et al., 2019) (Guyon et al., 2002) (Día­
z-Uriarte and Alvarez de Andrés, 2006).
It is difficult to analyze data in an omics dataset because it is com­
plex, high-dimensional, and heterogeneous. Deep Learning is a suitable Fig. 3. Architecture of AE.
technique for handling the omics dataset for the prediction of better
results. In a Deep Learning algorithm, the features are learned auto­ pooling layer for reducing the data size and fully connected layer to
matically from the original input data (Hinton and Salakhutdinov, classify the data (https://youtu.be/PmZp5VtMwLE). Fig. 2 shows the
2006). Deep learning methods include Feed Forward Neural Network architecture of Convolutional Neural Network.
(FFN), Convolutional Neural Network (CNN), Autoencoder(AE), and The Output of the new width of the convolution layer:
Recurrent Neural Network(RNN). These techniques are employed in W = (Wi − f + 2p)/s + 1 (4)
real-time genomics dataset applications such as genomics and sequence
analysis, medical image processing, biomarker discovery and patient The Output of the new height of the convolution layer:
categorization (Martorell-Marugán et al., 2019).
H = (Hi − f + 2p)/s + 1 (5)
Feed Forward Neural Network (FFN) is a hierarchical structure of
neural network and it consists of input layer with n dimensional vector, The Output of the new depth of the convolution layer:
L-1 multi hidden layers having n neurons each and one output layer
D=k (6)
consists of k classes. It processing the inputs with weight along with bias
and optimizing with backpropagation (https://youtu.be/AASR9­ where,
rOzhhA). Fig. 1 shows the architecture of Feed Forward Neural Network.
The Output function of FFN: k is number of filters,
f (x) = hL (x) = O(aL (x)) (1) s is stride,
p is padding,
where, f is filter and
hi is activation layer: Wi and Hi are weights and heights of the previous layer.

hi (x) = g(ai (x)) (2)

Autoencoder (AE) is a special type of Feed forward Neural Network
with encoder and decoder. The encoder encodes the input into hidden
ai is pre-activation layer:
information and decoder decodes the input again from hidden infor­
ai (x) = bi + Wi hi− 1 (x) (3) mation. This model is trained to minimize the loss function and it re­
constructs the input close to the original input (https://youtu.
wi is weight and bi is bias. be/wPz3MPl5jvY). Fig. 3 shows the architecture of Autoencoder.
Convolutional Neural Network (CNN) model is used to learn the The output function of AE:
multiple layers of kernel filters along with learning the weights of the
classifier. It consists of convolution layer for extracting the features; Xi = f (W * H + C) (7)

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U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

A feed-forward neural network was proposed to discover biomarkers

Fig. 4. Architecture of RNN
The hidden function of AE:
H = g(Wxi + b) (8)
where,
xi is an original input,
b is bias,
C is constant and
Xi is reconstructed input
Recurrent Neural Network (RNN) has a recurrent connection used for
handling the sequential information. The state vector is the intermediate
process in the RNN. It will compute the combination of current input
values and previous values stored in state vectors. The output is based
current input and past input (https://youtu.be/ym5qG-3kJ10). Fig. 4
shows the architecture of Recurrent Neural Network.
The Output function of RNN:
yt = f (Vsi + c) (9)
The state function of RNN:
si = f (Ux + Wsi− 1 + b) (10)
where,
W, U and V are parameters shared at each time step,
b is bias and c is constant.
2. Feed forward neural network based gene expression data
analysis methods
A multistage ensemble classification was proposed to classify the
gene expression cancer data. In the first stage, most informative genes
are extracted from the first hidden neural network, then take start as the
informative genes as input for the second neural network. This model
shows better classification accuracy for leukemia and colon datasets
(Singh et al., 2019). Deep Cancer subtype Classification (Deep CC) was
supervised classification framework for cancer classification and pre­
diction. This framework was used to categorize the gene expression for
13 independent datasets and the confusion matrix was calculated. The
results achieved better performance than Random Forest (RF), Support
Vector Machine (SVM), and Gradient Boosting Machine (GBM). This
proposed model was to learn the biological characteristics of different
molecular subtypes for patient samples and to be used for single pre­
diction (Gao et al., 2019).
in a breast cancer dataset. They used the lasso penalty to estimate the
parameters and the Youden’s J index to compare models. The simulation
result achieved more robust if Youden’s J index value decreases because
it will produce better sensitivity and specificity values when compared
to meta logistic regression methods and meta SVM methods (Lim et al.,
2019). A Deep Neural Network model was proposed to classify normal
and tumor samples of gene data and to learn the important character­
istics of gene data. These data were downloaded from GEO and TCGA
and the model achieved good classification accuracy for training and
independent testing datasets (Ahn et al., 2018). A Deep Flexible Neural
Network (DFNForest) model was suggested to solve many binary clas­
sification problems and to extend the flexible neural tree (FNT) without
adding additional parameters to increase the depth of the tree. Along
with fisher ratio and rough set, they were employed to minimize the
dimensions of gene data. The model achieved better results for the
classification of cancer subtypes such as breast, glioblastoma and lung
(Xu et al., 2019).
A preprocessing technique was applied to handle noisy and outlier
data before training the model. The proposed model was called
“improved DNN,” and it included Dropout in the DNN to avoid over­
fitting. The model was achieved better classification accuracy compared
to DNN, CNN and RNN (Ahmed and Brifcani, 2019). A Deep Neural
Network (DNN) model was proposed for feature selection in gene data
and for getting better classification results. Prior to the classification,
gene ranking is done to achieve a high performance in classification and
to improve the prediction accuracy. This model achieved a better ac­
curacy value compared to MLP, Nave Bayes and decision trees (Chan­
drasekar et al., 2020). A Grouping Genetic Algorithm (GGA) along with
an Extreme Learning Machine (ELM) was proposed to solve the grouping
problem for unbalanced gene expression datasets and to classify the
data. It achieved good generalization performance with extreme speed
for classification applications in multi-label datasets, dimensionality
reduction problems and regression applications. The proposed model
was achieved better accuracy to classify the 49 gene samples (García-­
Díaz et al., 2020).
Genome Deep Learning (GDL) was proposed to learn the relationship
between traits and genome variations for cancer identification in deep
neural networks. To train this model, the healthy samples are down­
loaded from the International Genome Sample Resource (IGSR) and
TCGA repository tumor samples are downloaded. This model was ach­
ieved better classification accuracy, sensitivity and specificity values.
For predicting better accuracy, we need to consider more factors in
genome variations like age, sex and proteome data (Sun et al., 2019). A
modified generator GAN (MG-GAN) model was proposed to generate
synthetic data using multivariate noise with a Gaussian distribution. The
proposed model uses latent space to specify the permissible region. DNN
was used to improve classification accuracy by optimizing the loss
function (Chaudhari et al., 2020). An improved KNN was proposed to
generate the synthetic samples based on each target end point. In the
proposed model, Euclidean distance, counting quotient filter and the
mean value of k nearest neighbors were calculated. DNN was used for
the classification of sample data, and it achieved better recall value and
also ensured the sensitivity (Chaudhari et al., 2021). Conditional GAN
was proposed as a sharp and accurate prediction for gene inference in
the target profiles. The proposed model engaged with ℓ1-norm loss and
adversarial loss functions to produce better regression results and
computed Mean Absolute Error and Concordance Correlation values for
GEO and GTEx datasets (Wang et al., 2018).
The Wasserstein generative adversarial network (WGAN) was a deep
learning approach used for cancer diagnosis for imbalanced datasets.
This model was a progress indicator and it was extremely useful for the
uniqueness of data. The proposed model predicted the gene data for
stomach, breast and lung tissues (Xiao et al., 2021). A multilayer FFN
was proposed to learn the existing non-linearity between the input space
and the output space. For feature selection of RNA Sequence data, the

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U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

Table 1
Feed Forward Neural Network (FFN) based gene expression data analysis methods.
Paper Ref. Dataset Method Performance Parameter Values
Technique Obtained

Singh et al. (2019) Benchmark Dataset: Leukemia and colon cancer FFN – Multistage Ensemble Classification Accuracy (Leukemia) 97.1%
Accuracy (Colon) 90.3%
Gao et al. (2019) MsigDB, The Cancer Genome Atlas (TCGA): Deep CC – Deep Cancer Classification Accuracy >90%
Colon and Breast Cancer Subtype Classification Sensitivity >95%
Specificity >95%
Lim et al. (2019) The Cancer Genome Atlas (TCGA): Breast Cancer FFN Prediction Learning Rate 0.9
Data Sensitivity 0.7770
Specificity 0.5229
Youden’s J index 0.3
Ahn et al. (2018) 1.GEO: Gene Expression Omnibus FFN Classification Training Dataset 0.997
2.TCGA: The Cancer Gene Atlas Independent Test data 0.979
3.TARGET: Therapeutically Applicable
Research To Generate Effective Treatments
4.GTEx:
Genotype-Tissue Expression
Xu et al. (2019) The Cancer Genome Atlas (TCGA) DFNForest- Deep flexible Classification Accuracy(BRCA) 0.936
neural forest Accuracy(GBM) 0.842
Accuracy (Lung) 0.880
Ahmed and 1.Kent Ridge Bio-medical Dataset: Leukemia and FFN with Dropout Classification Accuracy(DLBCL) 98.4%
Brifcani (2019) colon 2.Benchmark Dataset: DLBCL and Prostate Accuracy(Prostate) 93.2%
Accuracy(Leukemia) 99%
Accuracy(Colon) 91.4%
Chandrasekar et al. NCBI Repository FFN Classification Accuracy 72.5%
(2020)
García-Díaz et al. NCBI Repository FFN - GGA with ELM Classification Accuracy 98.81%
(2020)
Sun et al. (2019) 1. IGSR- The International Genome Sample FFN - GDL Prediction Accuracy >97%
Resource Sensitivity >98%
2. TCGA- The Cancer Genome Atlas Specificity >97%
Chaudhari et al. NCBI repository MG-GAN: Modified Generator Classification Accuracy(Lung) 88.1%
(2020) GAN Precision(Lung) 92.1%
Accuracy(Prostate) 93.6%
Precision(Prostate) 91%
Accuracy(Leukemia) 88.4%
Precision(Leukemia) 90.47%
Accuracy(Breast) 90.3%
Precision(Breast) 89%
Accuracy(Colon) 91.7%
Precision(Colon) 91.5%
Chaudhari et al. NCBI repository FNN & Improved KNN Classification Accuracy(Lung) 76.2%
(2021) Recall (Lung) 72%
Accuracy(Prostate) 81.4%
Recall (Prostate) 74.8%
Accuracy(Leukemia) 74.9%
Recall (Leukemia) 68%
Accuracy(Breast) 77.6%
Recall (Breast) 72%
Accuracy(Colon) 76.8%
Recall (Colon) 73%
Wang et al. (2018) 1.GEO FNN -Conditional Prediction Mean Absolute Error(MAE) 0.2897±0.0890
2.GTEx Generative Adversarial – GEO DATA
Network Concordance correlation 0.8785±0.0894
(CC) – GEO DATA
Mean Absolute Error(MAE) 0.4215±0.1264
– GTEx DATA
Concordance correlation 0.7475±0.2070
(CC) – GTEx DATA
Xiao et al. (2021) The Cancer Genome Atlas (TCGA): BRCA, STAD FNN- Wasserstein generative Prediction Accuracy(BRCA) 98.33%
and LUAD adversarial network(WGAN) Precision(BRCA) 100%
Recall(BRCA) 96.67%
F1(BRCA) 98.31%
AUC(BRCA) 0.98
Accuracy(STAD) 96.67%
Precision(STAD) 100%
Recall(STAD) 93.33%
F1(STAD) 96.55%
AUC(STAD) 0.97
Accuracy(LUAD) 96.67%
Precision(LUAD) 100%
Recall(LUAD) 93.33%
F1(LUAD) 95.55%
AUC(LUAD) 0.96
Urda et al. (2017) LASOO, DeepNeti, DeepNetii Prediction AUC(BRCA) – LASOO 0.65
(continued on next page)

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U. Ravindran and C. Gunavathi
Table 1 (continued )
Paper Ref. Dataset Method
The Cancer Genome Atlas (TCGA) –BRCA, COAD
and KIPAN
Park et al. (2021) The Cancer Genome FFN - GAN
Atlas (TCGA) -BRCA, LAML, LIHC,
LUAD, PAAD, STAD and LGG
LASSO method was used to adjust the gene expression data. Two
dimensionality reduction techniques DeepNeti and DeepNetii were used
to retrieve the most important genes (Urda et al., 2017). A deep
learning-based method was proposed, and it has three steps. First, the
GAN method was used to learn the prognostic specific networks for
omics data. Second, scoring was done for each patient data set in the
network. Third, a deep-feed forward neural network was used to predict
the patient’s prognosis (Park et al., 2021). The different methods used
for the gene expression data analysis using FFN is given in Table 1.
3. Convolutional neural network based gene expression data
analysis methods
Several CNN models were proposed to classify unstructured gene
expression and to distinguish between tumor and normal samples. 1-
Dimensional-CNN was used to process the vector input, 2-Dimen­
sional-Vanilla-CNN was used to extract the local features from 2-Dimen­
sional images and 2-Dimensional-Hybrid-CNN processes the 2D input
with a 1D kernel. These proposed models achieved improvement in
prediction accuracy from The Cancer Genome Atlas (TCGA) across 33
tumor classes and one normal class. The 1D-CNN produced the best
accuracy value among five subtypes in predicting the biomarkers of
breast cancer (Mostavi et al., 2020). A lightweight CNN model was
proposed to classify gene datasets for identifying breast cancer. The data
is downloaded from the Pan Cancer Atlas and then preprocessing was
done to remove the outlier samples and converted them into 2D images.
A normalization process was applied to ensure the correct gene
expression level and avoid biases. The proposed model achieved better
classification accuracy (Elbashir et al., 2019). The DeepGx method was
proposed to solve the classification problem of cancer data in the gene
expression dataset. The proposed method was to construct
two-dimensional images from the one-dimensional RNA-Sequence in­
formation. The CNN model was used for classification to find each gene
for each type and it improved the classification accuracy (Joseph et al.,
2019).
The Deep Learning Method was used for gene expression level pre­
diction in molecular biology. The drawback is to eliminate the current
structure for analyzing the evolutionary dependencies. The proposed
model has two approaches. The first approach was gene family guided
splitting, which is for training and testing of two different gene families,
and the second approach was ortholog contrasts, which is to compare
the orthologous genes for evolutionary during the training process
(Washburn et al., 2019). A multi-layer genome perceptron model was
developed to classify and group similar annotations in genomics data.
This proposed model was used to predict the breast cancer on normal
and tumor samples variations in gene expression level for improvement
in Estrogen Receptor (ER) status (Jha et al., 2018).
The CNN Model was proposed to identify the four subtypes of leu­
kemia from microscopic images. The data were downloaded from the
ALL-IDB and ASH Image Bank then applied data augmentation for
generating synthesis data for training. The CNN model achieved high
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Progress in Biophysics and Molecular Biology 177 (2023) 1–13
Performance Parameter Values
Technique Obtained
AUC(BRCA)- DeepNeti 0.62
AUC(BRCA) – DeepNetii 0.65
AUC(COAD) – LASOO 0.57
AUC(COAD)- DeepNeti 0.58
AUC(COAD) – DeepNetii 0.57
AUC(KIPAN) – LASOO 0.77
AUC(KIPAN)- DeepNeti 0.72
AUC(KIPAN) – DeepNetii 0.75
Prediction AUC 4%
improvement
AUC(pancreatic 27.9%
adenocarcinom) improvement
accuracy for normal and leukemia samples compared to machine
learning algorithms and also achieved better accuracy for subtypes of
multiclass classification (Ahmed et al., 2019). The CNN Model was
proposed to train the bone marrow images and to diagnose the Acute
Lymphoblastic Leukemia (ALL) subtypes. The proposed model achieved
better classification accuracy compared to other machine learning
classifiers like SVM, KNN, and Navie Bayesian (Rehman et al., 2018). In
convolution methods, the drawback is that they fail to differentiate the
various tumor types. The CNN model was proposed to train the 2-dimen­
sional images from the high-dimensional RNA sequence data and to
identify the specific tumor types. The data was downloaded from The
Pan-Cancer Atlas, which has abundant information for different tumor
types for classification. The model achieved a better accuracy rate (Lyu
and Haque, 2018).
A hierarchical based graph convolution network was proposed to
construct the gene interaction graph and similarity graph. Two graphs
are used to gather the neighborhood information of gene data. This
proposed model was to learn the better gene representation and perform
the downstream task with better performance. It achieved better clas­
sification performance when the training percentage was 70 (Tan et al.,
2021). To classify various tumor types on RNA-seq data a novel CNN
model was proposed, along with binary particle swarm optimization
with decision tree (BPSO-DT). It consists of three phases: data pre­
processing, data augmentation and data classification. The data pre­
processing phase involves using BPSO-DT to select the best features of
the RNA sequence and convert them into 2-D images. The data
augmentation phase consists of generating the synthesis data to improve
classification accuracy. The DeepCNN architecture phase extracts the
features from the images. This model achieved a better classification
accuracy result for BRCA, KIRC, LUAD, LUSC and UCEC tumor types
(Khalifa et al., 2020).
For data augmentation, Self-attention Progressive Growing of GANs
(SPGGANs) was proposed to generate skin lesion images based on
aggregated information in compact feature locations. The CNN model
was used for classification of the images to detect the melanoma and the
results achieved an improvement in sensitivity (Abdelhalim et al.,
2021). The DeepCNN architecture was proposed for the classification of
multi-grade brain tumors. In this model, first data augmentation tech­
niques are effectively applied to generate the data to avoid insufficient
data problems. Then the CNN model is used to train for non-augmented
and augmented data. The augmented data shows better classification
accuracy results for the Radiopaedia dataset and brain tumor dataset
(Sajjad et al., 2019).
The Gene Regulatory Interaction Prediction (Grip) along with the
Deep Learning (DL) method was proposed to predict the gene regulatory
networks (GRNs) for Drosophila embryonic gene expression images. It
achieved a better improvement in accuracy and F1 score compared with
stability-driven nonnegative matrix factorization (staNMF) (Yang et al.,
2019a). The CNN model was proposed for microarray gene data to
classify the seven different cancer datasets. This model achieved a better
classification accuracy result for brain and breast cancer data (Zeebaree
U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

Table 2
Convolutional Neural Network (CNN) based gene expression data analysis methods.
Paper Ref. Dataset Method Performance Parameter Values Obtained
Technique

Mostavi et al. The Cancer Genome Atlas (TCGA) 1D-CNN, 2D Vanilla Prediction Accuracy 93.9–95.0%
(2020) – CNN, Accuracy(Breast 88.42%
2D Hybrid- CNN cancer)
Elbashir et al. The Cancer Genome Atlas (TCGA): Breast Cancer Light Weight CNN Classification Accuracy 98.76%
(2019) Sensitivity 91.43%
Specificity 100%
Precision 100%
F-measure 0.955
Joseph et al. (2019) 1.TCGA DeepGx Classification Accuracy 95.65%
2.GEO
3.GTEx
Washburn et al. NCBI Repository CNN Prediction ROC curve Range from 0.75 to
(2019) 0.94
Jha et al. (2018) The Cancer Genome Atlas (TCGA): Breast Cancer GCNN Prediction GSE20685 AUC 91.7%
P 0.0231
Value
GSE25055 AUC 94.5%
P 0.44
Value
GSE22219 AUC 94.5%
P 0.001
Value
GSE12276 AUC 91%
P 0.011
Value
GSE7390 AUC 92.4%
P 0.05
Value
GSE24450 AUC 92.4%
P 0.029
Value
Ahmed et al. (2019) ALL-IDB and ASH Image Bank: Leukemia data CNN Classification Accuracy 88.25%
Accuracy(Multi 81.75%
Class)
Rehman et al. Amreek Clinical Laboratory: Leukemia data CNN Classification Accuracy 97.78%
(2018)
Lyu and Haque The Cancer Genome Atlas (TCGA) CNN Classification Accuracy 95.59%
(2018) Precision 95.54%
Recall 95.59%
F- Score 95.43%
Tan et al. (2021) UCSC Xena Repository CNN Classification Accuracy (Training 92.6%
Percentage 70)
Khalifa et al. (2020) The Cancer Genome Atlas (TCGA): BRCA, KIRC, LUAD, CNN Classification Accuracy(BRCA) 98.3%
LUSC and UCEC Accuracy(KIRC) 98.2%
Accuracy(LUAD) 84.8%
Accuracy(LUSC) 97.7%
Accuracy(UCEC) 96.4%
Abdelhalim et al. HAM10000- annotated skin lesion images GAN, CNN (DL) Classification Sensitivity 2.5%
(2021) Improvement
Sensitivity 8.6%
Improvement (For
melanoma class)
Sajjad et al. (2019) Radiopaedia dataset: 121 MR images CNN Classification Accuracy (For 90.67%
radiopaedia dataset)
Sensitivity (For brain 88.41%
tumor dataset)
Specificity (For brain 96.12%
tumor dataset)
Yang et al. (2019a) Benchmark dataset: ISH images GripDL Prediction Accuracy and F1 14% improvement
Score
Zeebaree et al. Benchmark dataset: Brain, Breast, Colon, Leukemia, CNN Classification Accuracy(Brain) 97.62%
(2018) stomach, prostate and lung datasets Accuracy(Breast) 97.69%
Accuracy(Colon) 64.52%
Accuracy(Leukeima) 100%
Accuracy(Lung) 72.09%

et al., 2018). The different methods used for the gene expression data
analysis using CNN is given in Table 2.
4. Autoencoder based gene expression data analysis methods
Multilayer Perceptron (MLP) with Stacked Denoising Autoencoder
(SAE) was a regression-based prediction model to measure gene
expression profiles and genotypes. SAE was used for feature selection for
the input as SNP genotypes and MLP were applied for backpropagation.
To avoid over-fitting and to improve performance for high-dimensional
data, a dropout was used during processing (Xie et al., 2017). The Deep
Subspace Fusion model was a clustering technique proposed to

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Table 3
Autoencoder (AE) based gene expression data analysis methods.
Paper Ref. Dataset Method Performance Parameter Values Obtained
Technique

Xie et al. Yeast data set Stacked Denoising Autoencoder Prediction Mean Square Error 0.2890
(2017) (MSE)
Correlation value of 0.3082
MSE
Yang et al. The Cancer Genome Deep Subspace Fusion Clustering (DSFC) Prediction Cox Log-Rank P- 7.02e-6 (No. of
(2019b) Atlas (TCGA): GBM,BIC, KRCCC, LSCC, COAD value (GBM) Cluster = 3)
and OV Cox Log-Rank P- 8.95e-4(No. of
value (BIC) Cluster = 4)
Cox Log-Rank P- 1.46e-3(No. of
value (KRCCC) Cluster = 3)
Cox Log-Rank P- 8.12e-4(No. of
value (LSCC) Cluster = 3)
Cox Log-Rank P- 7.95e-6(No. of
value (COAD) Cluster = 2)
Cox Log-Rank P- 4.03e-5 (No. of
value (OV) Cluster = 3)
Wu et al. SEQC neuroblastoma dataset – GEO database HetEnc Prediction Cross validation in 0.854
(2019) RNA Seq
Cross validation in 0.825
Microarray
Danaee et al. The Cancer Genome Stacked Denoising Autoencoder Classification Accuracy(ANN) 96.95%
(2017) Atlas (TCGA): Breast samples Sensitivity(ANN) 98.73%
Specificity(ANN) 95.29%
Precision(ANN) 95.42%
F-measure(ANN) 0.970
Accuracy(SVM) 98.04%
Sensitivity(SVM) 97.21%
Specificity(SVM) 99.11%
Precision(SVM) 99.17%
F-measure(SVM) 0.981
Accuracy (SVM- 98.26%
RBF)
Sensitivity(SVM- 97.61%
RBF)
Specificity(SVM- 99.11%
RBF)
Precision(SVM- 99.17%
RBF)
F-measure(SVM- 0.983
RBF)
Guan et al. KEGG PATHWAY and PubMed Central Stacked Denoising Autoencoder Multi- Classification Coverage precision 0.577
(2018) Label Learning (SdaMLL) Ranking loss 0.286
Coverage 2.436
Jiang et al. Blood pressure data from the MIMIC-II Autoencoder Prediction Accuracy 88.14%
(2021) database
Xie et al. Yeast data set Stacked Denoising Auto-encoder Prediction Average MSE 0.3082
(2016)
Liu et al. IBC dataset: Sample Expansion Method with Classification Accuracy(Breast)- 87.33%
(2017) Colon, Leukemia and Breast Autoencoder and 1DCNN SESAE
Accuracy 49.79%
(Leukemia)- SESAE
Accuracy(Colon)- 84.42%
SESAE
Accuracy(Breast)- 95.33%
SE1DCNN
Accuracy 57.87%
(Leukemia)-
SE1DCNN
Accuracy(Colon)- 84.90%
SE1DCNN
Karim et al. The Cancer Genome Convolutional LSTM, Convolutional Prediction Accuracy(CLSTM) 74.25%
(2020) Atlas (TCGA) autoencoder and Model averaging Accuracy(CAE) 78.32%
ensemble (MAE) MAE 2.5% improvement
Pirmoradi et al. NCBI Repository: (GEO database) GSE67047, Self-organizing auto-encoder (SOAE) Classification Accuracy(Thyroid 100%
(2020) GSE13117, GSE16619, GSE34678 and Cancer)
GSE9222 F-measure(Thyroid 100%
Cancer)
Specificity(Thyroid 100%
Cancer)
Sensitivity(Thyroid 100%
Cancer)
Accuracy (Mental 94.4%
Retardation)
(continued on next page)

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U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

Table 3 (continued )
Paper Ref. Dataset Method Performance Parameter Values Obtained
Technique

F-measure (Mental 93.1%

Retardation)
Specificity (Mental 93.2%
Retardation)
Sensitivity (Mental 96.4%
Retardation)
Accuracy(Breast 100%
Cancer)
F-measure(Breast 100%
Cancer)
Specificity(Breast 100%
Cancer)
Sensitivity(Breast 100%
Cancer)
Accuracy 96%
(Colorectal Cancer)
F-measure 96.3%
(Colorectal Cancer)
Specificity 91.7%
(Colorectal Cancer)
Sensitivity 100%
(Colorectal Cancer)
Accuracy (Autism) 99.1%
F-measure(Autism) 99.2%
Specificity(Autism) 100%
Sensitivity(Autism) 98.5%
Zhang et al. NCBI Repository: (GEO database) GSE2990, Linear Discriminant Analysis (LDA) and Prediction Accuracy 98.27%
(2020) GSE3494, GSE9195, GSE17705 and Autoencoder (AE)
GSE17907
Seal et al. The Cancer Genome Deep Denoising Autoencoder (DDAE) Classification Accuracy 95.1%
(2020) Atlas (TCGA): Liver data

differentiate the gene expression similarity between patient samples to
achieve effective results. It adopts DNN to expose each type of feature.
Similarity Network Fusion (SNF) was applied to measure the similarity
between patients using Euclidean distances and to obtain the final result
spectral clustering was done (Yang et al., 2019b). The HetEnc model was
proposed to handle platform-independent gene datasets for both su­
pervised and unsupervised networks. For extracting the features, they
used three encoding networks: Autoencoder (AE), CombNET and
CrossNET. A 6 layered DNN was used for predicting the output of each
targeted endpoint (Wu et al., 2019).
A stacked denoising autoencoder was proposed to obtain meaningful
information from gene data in the TCGA dataset. ANN, SVM, and
SVM–RBF supervised classification models were used to evaluate the
value of extracted features for breast cancer cell detection (Danaee et al.,
2017). A Stacked Denoising Autoencoder (SDA) with Multi-Label
Learning (MLL) architecture was proposed to predict the gene
pathway analysis. SDAE was used to remove the various noises from the
original vector in the feature matrix. Then the output of the stacked
denoising autoencoder is fed into BP-MLL for pathway prediction. The
result achieved good performance in coverage precision value compared
to traditional multi-label algorithms (Guan et al., 2018). The hybrid
deep learning model was proposed for acute hypotensive episode (AHE)
detection. For processing the AHE signal, a single decomposition
method was used, and for feature extraction, an autoencoder was used.
The result achieved good classification accuracy for patient samples
(Jiang et al., 2021). A Multi-Layer Perceptron (MLP) with a Stacked
Denoising Autoencoder (SAE) was proposed to train the model to
retrieve the meaningful features and predict the gene value of an SNP
genotype. To improve the model, backpropagation is applied to the
multilayer perceptron and to prevent the overfitting problem, dropout
techniques were added. The proposed model outperforms than model
without dropout and traditional methods such as Random Forest and
Lasso (Xie et al., 2016).
In the gene expression data, the Sample Expansion method was
proposed for effective classification of tumor samples. To generate the
synthesis samples a denoising autoencoder was used to corrupt the input
data. For the classification of data samples, 1D-CNN was used. These
models achieved better accuracy values (Liu et al., 2017). Before cancer
occurs, copy number variations (CNVs) are utilized to define genetic
features. The ensemble method was proposed to predict the cancer
types. Convolutional LSTM and convolutional autoencoder were pro­
posed for two different sparse representations that were developed to
train and capture important features. A snapshot ensemble method was
used to make the single prediction with better accuracy. (Karim et al.,
2020).
To analyze the Single Nucleotide Polymorphism (SNP) genomics
data for classifying the patient samples effectively, the deep Autoen­
coder model was proposed. For preprocessing the data, the mean
encoding method was used to convert the numeric values from the SNP
and the filter method was applied to remove redundant and irrelevant
features. The proposed model was a Self-organizing auto-encoder
(SOAE) used to classify the samples and achieved better classification
accuracy for different types of cancer datasets (Pirmoradi et al., 2020).
To classify the different features in the gene expression profile with a
low-intensity ratio, the authors proposed an Autoencoder (AE), along
with a linear discriminant analysis approach. This proposed model was
used on different breast cancer independent datasets to achieve better
prediction accuracy (Zhang et al., 2020). The Deep Denoising
Auto-encoder (DDAE) was a predictive model used to handle omics data
in various platforms, like epigenetic and genetic data. The DDAE was
applied to train the gene data and extract the important features. A
Multi-layer Perceptron (MLP) was used for backpropagation. These
models achieved better classification accuracy for gene expression
datasets (Seal et al., 2020). The different methods used for the gene
expression data analysis using AE is given in Table 3.
5. Recurrent neural network based gene expression data
analysis methods
A recurrent network and convolutional network architectures were

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U. Ravindran and C. Gunavathi Progress in Biophysics and Molecular Biology 177 (2023) 1–13

Table 4
Recurrent Neural Network (RNN) based gene expression data analysis methods.
Paper Ref. Dataset Method Performance Parameter Values Obtained
Technique

Zheng et al. (2020) miRBase and NCBI Repository RNN Prediction Accuracy 90%
Specificity 90%
Immaculate NCBI Repository LSTM and KNN Prediction Accuracy 0.945
MercyChidambaram Running Time 0.14
(2020)
Kishan et al. (2019) BioGRID repository Gene Network Embedding Prediction AUROC (Yeast) 0.710
(GNE) –One hot AUPR (Yeast) 0.983
Representation AUROC (E Coli) 0.653
AUPR (E Coli) 0.658
Bychkov et al. (2018) The Hospital District of Helsinki and Uusimaa CNN, LSTM Prediction Hazard ratio 2.3
AUC 0.69
Zhao et al. (2019) Benchmark Dataset (scRNA): 1.Data1- primitive RNN Classification AUROC (Data1) 0.620
endoderm (PrE) cells 2.Data2- mouse embryonic AUROC (Data2) 0.587
fibroblast (MEF) cells 3.Data3- definitive endoderm AUROC (Data3) 0.578
(DE) cells
Liu and Liu (2020) Benchmark Dataset: DREAM3 and DREAM4 MALASSORNN-GRN Classification AUROC (node = 0.6351
10, Density =
20%)
AUROC (node = 0.7188
10, Density =
40%)
Majji et al. (2021) GEMLeR repository: AP_Colon_Kidney data, JayaALO-based DeepRNN Classification Accuracy 95.97%
AP_Breast_Ovary data, AP_Breast_Colon data, Sensitivity 95.95%
AP_Breast_Kidney data Specificity 96.96%
Chowdhury et al. (2019) Benchmark Dataset: Colon and Leukemia GRU, LSTM, RNN and Classification F1 score 11% and 15% (DT
bidirectional LSTM. and NB
Classifiers)
Şahín and Diri (2019) Gene expression profile (GEP) datasets: COLON, LUNG, LSTM based AIRS Classification Average Accuracy 92.8%
PROSTATE, SRBCT, LYMPHOMA, AND LEUKEMIA
Suresh et al. (2021) NCBI Repository LSTM Classification Accuracy 86.36%
Aher and Jena (2021) 1.UCI Health Repository:Lung cancer RCO-RNN Classification Accuracy 94.5%
2.Computer Age Statistical Inference: Leukemia cancer (Leukemia)
3.Bioinformatics Lab:SBRCT cancer Sensitivity 94.5%
(Leukemia)
Specificity 94.7%
(Leukemia)
PPV(Leukemia) 94.5%
NPV(Leukemia) 94.5%
Accuracy(SBRCT) 94.0%
Sensitivity 94.0%
(SBRCT)
Specificity 94.0%
(SBRCT)
PPV(SBRCT) 94.0%
NPV(SBRCT) 94.0%
Accuracy(Lung) 95.0%
Sensitivity(Lung) 95.0%
Specificity(Lung) 95.0%
PPV(Lung) 95.0%
NPV(Lung) 95.0%

applied to automatically learn characteristics from RNA-seq and detect
human miRNA. The RNN model consists of three LSTM layers to
remember or ignore the past information. The model achieved good
prediction accuracy and sensitivity values for the human pre-miRNA
dataset (Zheng et al., 2020). Long short-term memory (LSTM) is a
RNN approach that was proposed for the classification of gene expres­
sion data. LSTM was combined with K-Nearest Neighbour (KNN) to
perform better classification performance. For feature selection, prin­
cipal component analysis and the CHI square test were used. The pro­
posed model shows a better accuracy value and also reduces the running
time compared to existing traditional methods (Immaculate MercyChi­
dambaram, 2020). The Gene Network Embedding (GNE) framework was
used to combine the gene expression data and gene interaction network.
The proposed model was used to learn the embedded representation and
to predict the gene interactions from heterogeneous datasets. Deep
embeddings yielded substantially more accurate predictions, according
to the findings. (Kishan et al., 2019).
An ensemble method was used for classifying and predicting tumor
and normal samples. CNN and RNN architectures were used. The
appropriate features from the input vector were extracted using a
convolution network. LSTM was used to predict the risk score for the
patient. (Bychkov et al., 2018). A RNN model was proposed to train the
gene data and to identify the transcriptional target factor with better
accuracy. The AUROC was measured for three different datasets and
transferred from the Gene Regulatory Network to binary classification
(Zhao et al., 2019). Optimizing gene regulatory networks (GRNs) is a
challenging problem because the relationships between genes are spared
in the dataset. To overcome the problem, a MALASSORNN-GRN model
was proposed for achieving the best results. The memetic algorithm was
applied to learn the parameters of the recurrent network and LASSO was
used for reconstructing the GRNs (Liu and Liu, 2020).
The Jaya Ant Lion optimization model was proposed for gene
expression data preprocessing. First, data normalization was used to
remove the redundant data. Second, data transformation was used to
generate the patterns, and third, factorization was used for feature
reduction. Finally, a recurrent neural network model was employed for
the classification of the cancer (Majji et al., 2021). Several RNN
frameworks were proposed for feature selection of micro array gene

9
U. Ravindran and C. Gunavathi
Fig. 5. Accuracy value obtained from different Deep Learning Methods:
a: Accuracy value obtained from Feed forward Neural Network (FFN) b: Ac­
curacy value obtained from Convolutional neural network (CNN) c: Accuracy
value obtained from Autoencoder (AE) d: Accuracy value obtained from
Recurrent Neural Network (RNN).
expression datasets. These frameworks were RNN, LSTM, bidirectional
LSTM and GRU. These frameworks were mostly applied to choose the
most important characteristics. Traditional machine learning algorithms
were used for classification tasks. The results achieved an improvement
in F1-Score value (Chowdhury et al., 2019).
10
Progress in Biophysics and Molecular Biology 177 (2023) 1–13
Fig. 6. Accuracy value obtained from different types of cancer:
a: Accuracy value obtained from Breast cancer b: Accuracy value obtained from
Lung cancer c: Accuracy value obtained from Leukemia cancer d: Accuracy
value obtained from Colon cancer.
The Long Short Term Memory (LSTM) with the artificial immune
recognition system (AIRS) algorithm was used to effectively find the
most significant features in the gene expression data. AIRS was used to
remember the long sequences and LSTM was used to map the sequential
features. This algorithm achieved a better accuracy for different
microarray gene expression datasets (Şahín and Diri, 2019). Genomic
U. Ravindran and C. Gunavathi
Fig. 7. Sensitivity, Specificity, Precision, F- Measure average values retrieved
from existing deep learning methods:
a: Sensitivity value retrieved from Deep Learning Methods b: Specificity value
retrieved from Deep Learning Methods c: Precision value retrieved from Deep
Learning Methods d: F-Measure value retrieved from Deep Learning Methods.
sequencing was primarily used in cancer treatment to identify infected
individuals who had risk factors and complaints in their human cells. An
LSTM with an optimization approach was proposed for predicting can­
cer disease using genome sequencing. For optimization, an Adaptive Bat
Sonar Algorithm was used. This approach achieved a higher accuracy
when compared to hybrid classifiers (Suresh et al., 2021). A Rider
11
Progress in Biophysics and Molecular Biology 177 (2023) 1–13
Chicken Optimization with Recurrent Neural Network (RCO-RNN) al­
gorithm was proposed to identify the tumor using gene data. For
selecting the gene features, entropy was used to reduce the dimension­
ality. The proposed algorithm was used to train the gene features and
classify the data. In confusion matrix the results are achieved with better
performance and maximum value (Aher and Jena, 2021). The different
methods used for the gene expression data analysis using RNN is given in
Table 4.
6. Discussion
In this review paper, we have analyzed the existing research works
which utilized deep learning methods for cancer diagnosis using gene
expression dataset. In the existing literature, the majority of gene data is
downloaded from the TCGA, GEO and NCBI repositories. In many
existing literature papers, the accuracy (Acc), sensitivity (Sen), speci­
ficity (Spe), precision (Prec), and F1 score values are calculated. Fig. 5
shows the accuracy values obtained from different deep learning
methods. Fig. 5a shows the accuracy values obtained from the feed-
forward neural network. The maximum accuracy of 99.7% was ach­
ieved using FFN. Fig. 5b shows the accuracy values obtained from the
convolutional neural network. The maximum accuracy of 98.76% was
achieved using CNN. Fig. 5c shows the accuracy values obtained from
the autoencoder. The maximum accuracy of 98.27% was achieved using
AE. Fig. 5d shows the accuracy values obtained from the recurrent
neural network. The maximum accuracy of 95.97% was achieved using
RNN.
Fig. 6 shows the accuracy values obtained from different types of
cancer dataset using deep learning methods. Fig. 6a shows the accuracy
values obtained from the breast cancer dataset. The maximum accuracy
achieved was 100%. Fig. 6b shows the accuracy values obtained from
the lung cancer dataset. The maximum accuracy achieved was 97.7%.
Fig. 6c shows the accuracy values obtained from the leukemia cancer
dataset. The maximum accuracy achieved was 100%. Fig. 6d shows the
accuracy values obtained from the colon cancer dataset. The maximum
accuracy achieved was 91.7%.
Fig. 7 shows the average value obtained for Sensitivity, Specificity,
Precision, and F- Measure using deep learning methods. Fig. 7a shows
the sensitivity values obtained and the maximum sensitivity achieved
was 98.98%. Fig. 7b shows the specificity values obtained and the
maximum specificity achieved was 100%. Fig. 7c shows the precision
values obtained and the maximum precision achieved was 100%. Fig. 7d
shows the F-measure values obtained and the maximum F-measure
achieved was 98.98%.
7. Conclusion
Microarray or RNA sequence Gene expression data is especially used
for cancer disease diagnosis and prediction. The curse of dimensionality
problem occurs in gene expression datasets for classifying and predicting
cancer samples and their types. Data augmentation techniques are
applied in most of the papers to solve the dimensionality problem for
gene expression datasets. Data preprocessing was applied in most of the
papers to remove the redundant data and noisy data. For extracting the
relevant features from the gene expression dataset, the feature selection
and feature extraction methods were used. Deep learning algorithms
were used to classify and predict cancer disease and its types and
compare the results with traditional algorithms. This survey paper has
mainly focused on analyzing gene expression datasets on feed-forward
neural network, convolutional neural network, autoencoder and recur­
rent neural network based deep learning methods.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
U. Ravindran and C. Gunavathi
the work reported in this paper.
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