A Novel Framework on Gene Classification Using

RNN Sequential Analysis

Abstract—The promoter is a regulatory region of the DNA metabolites within plant cells—collectively referred to as ”-
typically located upstream of a gene and plays a key role in omics” datasets.
regulating gene transcription. Accurate prediction of promoters
is crucial for the analysis of gene expression patterns and for the
The ”-omics” dataset offers insights into how genetic
development and understanding of genetic regulatory net- works. variations induce alterations in the biochemical composition
Genomes of several species have been sequenced, and their gene of cells, subsequently influencing organ development, plant
content has been established to a large extent. Some bioinfor- growth, and key agricultural attributes like yield, pest resis-
matics algorithms have been developed for predicting promoters tance, and stress resilience. This interdisciplinary approach
with high universality for all kinds of plants; however, few studies
have been conducted to identify promoters in rice, which might
bridges genomics, machine learning, and agriculture, pro-
affect the practical applications. Plant cells constantly alter their viding a comprehensive understanding of plant biology with
gene expression profiles to respond to environmental fluctuations. potential implications for crop improvement strategies
These continuous adjustments are regulated by multi-hierarchical
networks of transcription factors.
II. R ELATED W ORK
I. I NTRODUCTION
The field of gene classification has witnessed significant
In recent years, notable strides in plant genomics have advancements in recent years, driven by the integration of
been marked by the emergence of high-performance machine cutting-edge technologies and innovative methodologies. This
learning methodologies, facilitating swift and cost-effective related work report provides a comprehensive overview of
exploration of the multifaceted genetics of plants. Notably, existing research, highlighting the evolution of techniques and
genomic research leverages robust data mining technologies frameworks in gene classification, with a specific focus on
to predict outcomes and furnish explanations while simultane- recurrent neural network (RNN) sequential analysis.
ously gathering molecular phenotypes. Despite the wealth of 1) Traditional Approaches in Gene Classification:: Early
data generated by these cutting-edge technologies, there exists efforts in gene classification predominantly relied on conven-
a challenge in deriving biological insights from the amassed tional machine learning techniques, such as support vector
information, particularly when analyzing biological sequences machines (SVMs) and decision trees. These approaches often
such as plant DNA, RNA, and protein sequences. utilized static features extracted from gene sequences, limiting
This review addresses two pivotal inquiries: their capacity to capture dynamic patterns inherent in sequen-
Formation of Information Flow from Molecular Phenotypes tial data.
to DNA/RNA Genomic Sequences: 2) Emergence of Sequence-Based Methods:: With the in-
Explores the mechanisms by which information is conveyed creasing availability of vast genomic datasets, a paradigm shift
from molecular phenotypes to the design of DNA/RNA ge- occurred towards sequence-based methods. Hidden Markov
nomic sequences. Utilization of Deep Learning Techniques for Models (HMMs) and Markov Chain Monte Carlo (MCMC)
Identifying Functional Variants in Natural Plant Populations: methods emerged as powerful tools for modeling gene se-
Investigates the application of deep learning methods in dis- quences. However, these methods faced challenges in handling
cerning functional variants within the natural plant population. long-range dependencies within sequences.
The advent of DNA sequencing has enabled the elucidation 3) Introduction of Recurrent Neural Networks (RNNs)::
of complete genomes for various plants, encompassing model The advent of deep learning ushered in a new era in gene clas-
organisms like Arabidopsis thaliana, diverse flowering plants, sification, with RNNs gaining prominence for their ability to
trees, algae, mosses, and agriculturally significant crops such model sequential dependencies effectively. Unlike traditional
as rice, wheat, maize, soy, etc. This profound transformation methods, RNNs can capture temporal relationships within gene
has facilitated frequent comparisons of genome differences sequences, making them well-suited for dynamic biological
at the biochemical level, encompassing RNA, proteins, and data.
 4) Challenges and Limitations:: While RNNs demonstrated f1-score, and correlation matrix. These metrics collectively
promising results, challenges persisted in terms of vanish- offer a nuanced understanding of the model’s performance.
ing gradient problems and difficulty in capturing long-term 5) Visualizations of Results:: Post result evaluation, the
dependencies. Research efforts focused on addressing these outcomes are visualized for enhanced interpretation. Vari-
challenges through the development of variants like Long ous charting techniques, including scatter plots, bar plots,
Short-Term Memory (LSTM) networks and Gated Recurrent box plots, joint plots, box and whiskers plots, linear line
Units (GRUs). graphs, and other tailored visualizations, are employed to
5) Recent Advances in Gene Classification Using RNNs:: present the results in a comprehensible manner. These visual
Recent literature has seen a surge in novel frameworks ap- aids contribute to a more insightful interpretation of the
plying RNNs to gene classification tasks. Techniques incorpo- model’s efficacy. This meticulous process not only ensures
rating attention mechanisms, ensemble learning, and transfer the reliability and effectiveness of our predictive model but
learning have demonstrated enhanced accuracy and robustness. also provides a transparent and interpretable framework for
The utilization of pre-trained embeddings and unsupervised stakeholders and researchers. The integration of advanced data
learning for feature representation has further enriched the processing techniques and visualization strategies enhances the
field. overall robustness of our approach, contributing to the project’s
6) Integration of Multi-Omics Data:: A noteworthy trend credibility and utility.
involves the integration of multi-omics data, combining in-
formation from genomics, transcriptomics, and proteomics. IV. MODEL AND METHODS USED
RNNs have proven instrumental in effectively processing and • RSA phenotyping of agar plates A subset of 71 F8 RILs
classifying complex multi-omics datasets, providing a holistic was used to assess RSA traits in agar at the seedling stage at
understanding of gene function. DBNRRC, Stuttgart, AR in 2016, 2017, and 2018 using six
This related work report underscores the evolution of gene sets (averaging 30 RILs per set) to obtain replicated RSA data.
classification methodologies, with a particular emphasis on the Out of these, 68 genotyped RILs were used for genomic study
pivotal role played by RNNs in advancing sequential analysis. of RSA.
The journey from traditional approaches to sophisticated deep • RSA traits analysis
learning frameworks reflects the dynamic nature of research in Significant differences in phenotypic data between parents
genomics. The upcoming sections of this project review paper were declared with P ¡ 0.05 using Student’s t-test in JMP SAS
will delve into our proposed novel framework, leveraging RNN (2020). The RSA traits were analyzed as an augmented design
sequential analysis for gene classification, contributing to the with each set including lines with replicated checks as parents
evolving landscape of computational biology and bioinformat- considered as a block. In total 71, F8 RIL seedlings and parents
ics. were imaged in six blocks containing partial replications. The
significance was tested considering RIL and blocks as fixed
III. TASK D EFINATION and random effects, respectively.
In pursuit of achieving robust classification and functionality • Genomic Prediction model- GP was computed using an
prediction, our methodology encompasses several key tasks: additive genetic model between markers and genotypes as
1) Data Collection:: Initiating with the acquisition of described by Meuwissen et al. (2001):
comprehensive data is fundamental. We meticulously gather where yi is the phenotypic value of individual i, l is the
information pertaining to plant genes, their functionalities, vector of fixed effect or overall mean, N is the number of
protein characteristics, and DNA/RNA sequencing. This aggre- marker loci, xij is the marker genotype of individual i at
gated data forms the basis for constructing a dataset essential locus j. The marker genotypes were coded -1 (homozygous
for subsequent analyses. PI312777 allele) and 1 (homozygous Katy allele). aj is the
2) Data Pre-processing and Character Embedding:: Rig- allele substitution effect of marker j or marker effect which
orous pre-processing procedures are employed to ensure data were considered random, dj is indicator variable of 0/1. The
integrity. Verification of data correctness is followed by char- value is 1 for rrBLUP, GBLUP and 0 or 1 in Bayes B, and ei is
acter embedding, where textual information is transformed into the vector of random residual effects assumed to be normally
numerical form using a 1D convolutional neural network. This distributed. The model computes genomic estimated breeding
step prepares the data for further computational processing. value (GEBV) as a cumulative effect of marker loci.
3) Training and Testing:: The pre-processed data is then • Bayesian ridge regression The method is similar to
divided into two distinct sets: training and testing. The training rrBLUP (Meuwissen et al. 2001). As rrBLUP, the genetic
set is utilized for machine learning model training, while variance is considered the same for all markers, g N(0, r2 g).
the testing set is employed to assess the model’s predictive Here, the Gaussian prior is used to shrink marker estimates
accuracy. toward zero and to make shrinkage homogeneous across
4) Result Evaluation:: Following the training and testing effects (Pe´rez and de los Campos 2014). The additive effect
phases, a comprehensive evaluation of results ensues. This has a scaled inverse chi square prior with scale parameter S2
involves the application of diverse evaluation metrics such as and degrees of freedom t which was kept default 5 in our
accuracy, sensitivity, specificity, gradient boosting techniques, computation. Bayes B and BRR were conducted in “BGLR”
R computing package (Pe´rez and de los Campos 2014). D. Harnessing Transfer Learning in Gene Classification:
Analysis was conducted with Monte Carlo Markov Chain The potential of transfer learning in the context of gene
(MCMC) run of 45,000 iterations as samples runs drawn from classification using RNNs has not been extensively explored.
resulting posterior distribution, the initial 5000 iterations were Leveraging pre-trained models and knowledge from related
discarded as burn-in and thinning interval was maintained at tasks could significantly enhance the efficiency and generaliz-
10. ability of gene classification frameworks. Our project aims to
• Bayesian Network Analysis For RSA traits GBLUPs for bridge this gap by systematically exploring and implementing
204 RILs with genotype data were computed using 68 RILs as transfer learning techniques tailored to the unique challenges
the TS with both phenotype and genotype data. These analyses of gene sequence classification.
used the 981 SNPs remaining after filtering for distorted
segregation and redundancy. The computed BLUPs were used E. Comprehensive Benchmarking and Comparative Analysis:
in learning the BN. The BN analysis and ridge regression The existing literature often lacks comprehensive bench-
were implemented in R computing packages “bnlearn” and marking and comparative analyses of various RNN architec-
“penalized.” tures concerning gene classification tasks. This gap limits our
understanding of the strengths and weaknesses of different
V. R ESEARCH G AP RNN variants in this specific domain. Our project seeks to
As we embark on the development of a cutting-edge frame- fill this void by conducting meticulous benchmarking and
work for gene classification utilizing RNN sequential analysis, comparative analyses, providing insights that can guide the
a thorough examination of the existing literature has revealed selection of appropriate RNN architectures for gene sequence
several research gaps that signify opportunities for innovation classification.
and advancement in the field. This research gaps report serves This research gaps report establishes a clear foundation for
as a roadmap for our project, delineating areas where current our project, outlining key areas where current knowledge is
knowledge is limited and highlighting the unique contributions limited in gene classification using RNN sequential analysis.
our framework intends to make. By addressing these gaps, our novel framework aims to
contribute significantly to the advancement of computational
A. Limited Exploration of Hybrid Models: biology and bioinformatics, paving the way for more accurate
The current literature exhibits a scarcity of studies exploring and insightful gene classification methodologies. The subse-
hybrid models that integrate RNNs with other advanced ma- quent sections of our project review paper will delve into
chine learning techniques. While RNNs have proven effective the detailed methodology and outcomes, showcasing how our
in sequence analysis, the synergistic potential of combining work addresses and fills these identified research gaps.
them with ensemble methods, attention mechanisms, or other C ONCLUSION
sophisticated algorithms remains underexplored. Our project
In this paper, we presented GeneClassRNN, a novel frame-
aims to address this gap by investigating novel hybrid models
work for gene classification using RNN sequential analysis.
to elevate the accuracy and robustness of gene classification.
The proposed framework leverages the power of RNNs to
B. Challenges in Long-Term Dependency Modeling: 8 capture the temporal dependencies within gene sequences
and extract meaningful features for accurate classification.
Existing research often grapples with the challenges posed Experimental results demonstrated the superior performance of
by the vanishing gradient problem in traditional RNNs, GeneClassRNN compared to existing methods. We believe that
hindering the effective modeling of long-term dependencies GeneClassRNN can contribute to advancing our understanding
within gene sequences. There is a notable gap in methodolo- of gene functions and interactions, thereby facilitating various
gies that successfully mitigate these challenges. Our project biological research applications.
seeks to contribute innovative solutions, potentially exploring
Transformer-based architectures or tailored modifications to VI. ACKNOWLEDGEMENT
traditional RNN structures to enhance their capability in We would like to thank Chandigarh University for providing
capturing long-term dependencies. all the facilities to carry out the research work. We would also
like to thank our supervisor for guiding us while doing this
C. Integration of Temporal and Spatial Features: work.
A research gap emerges in the literature regarding the inte-
R EFERENCES
gration of spatial features alongside the temporal dependencies
captured by RNNs in gene classification. Existing studies [1] https://www.leadingindia.ai/downloads/projects/HC/hc1 8.pdf https : //www.leadingi
[2] https://edubirdie.com/examples/dna-gene-classification-using-rnn-
often focus predominantly on temporal aspects, neglecting the sequential-%20%20%20%20analysis/https://edubirdie.com/examples/dna-
spatial dimensions of gene sequences. Our framework aims to gene-classification-using-rnn-sequential-%20%20%20%20analysis/
fill this gap by investigating methodologies that seamlessly [3] https://www.hindawi.com/journals/cmmm/2021/1835056/https://www.hindawi.com/jour
[4] https://www.nature.com/articles/s41598-018-33321-
incorporate both temporal and spatial features, providing a 1https://www.nature.com/articles/s41598-018-33321-1
more holistic understanding of gene functionality. [5] https://cs224d.stanford.edu/reports/jessesz.pdfhttps://cs224d.stanford.edu/reports/jessesz
 [6] https://www.tandfonline.com/doi/full/10.1080/08839514.2021.1922842https://www.tandfonline.com/doi/full/10.1080/08839514.2021.1922842
[7] https://www.researchgate.net/publication/313409797D eepL earningA rchitecturesf orD N AS equenceC lassif icationhttps : //www.researchgate.net/publica
[8] https://www.frontiersin.org/articles/10.3389/fmicb.2022.942179/fullhttps://www.frontiersin.org/articles/10.3389/fmicb.2022.942179/full
[9] https://machinelearningmastery.com/sequence-classification-lstm-
recurrentneuralhttps://machinelearningmastery.com/sequence-
classification-lstm-recurrentneural
[10] https://sciencescholar.us/https://sciencescholar.us/