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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>International Conference on Computer and Intelligent Control, June</journal-title>
      </journal-title-group>
    </journal-meta>
    <article-meta>
      <title-group>
        <article-title>Research on protein complex recognition method based on genetic algorithm</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Zhiqiang Liu</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Yulan Tang</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Chongqing Sino Konjac Biotechnology Co.</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Chongqing</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>China</string-name>
        </contrib>
      </contrib-group>
      <pub-date>
        <year>2024</year>
      </pub-date>
      <volume>2</volume>
      <fpage>9</fpage>
      <lpage>30</lpage>
      <abstract>
        <p>In the rapid development of social economy and science and technology, how to study the interaction between proteins to complete the law of life activities has been one of the hot topics in academic research. Since protein interaction network is a typical complex network, which directly presents a significant social structure, and the corresponding functional modules are regarded as protein complexes, the corresponding identification and research methods have a positive role in predicting protein functions and explaining specific biological processes. Therefore, after understanding the research status of protein interaction network at home and abroad, this paper clarifies the protein complex recognition algorithm based on genetic algorithm according to the basic concept of protein interaction network, and then verifies the application value of the algorithm through experimental research, so as to provide reference for the application of the algorithm in the new era.</p>
      </abstract>
      <kwd-group>
        <kwd>genetic algorithm</kwd>
        <kwd>Protein complex</kwd>
        <kwd>Interaction</kwd>
        <kwd>Select strategy</kwd>
        <kwd>Crossover strategy</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introducion</title>
      <p>Under the background of the comprehensive promotion of the human Genome Project, life
science research has entered the post-genome era, and proteomics research is one of the
key contents. As early as the early 1990s, some scholars proposed the basic concept of
proteome, which refers to the collection of all proteins produced by a gene or variable
RNA splicing and post-transcriptional modification of mRNA expressed by a cell or tissue.
In other words, a collection of proteins expressed under certain conditions, at a certain
moment and in a certain type of cell or organism. In the process of research and
exploration, protein organization includes basic function, post-translational modification,
protein identification and</p>
      <p>
        many other contents. Proteomics theory and related
technologies can be used to accelerate the development of molecular medicine, truly serve
human life and health, and provide reference for the design of drugs that act on specific
target molecules. Protein is a biological macromolecule that occupies a special position in
the biological body. It is composed of a variety of amino acids according to dehydration
condensation according to a specific method. After winding and folding of polypeptide
chains, polymer compounds with a certain spatial structure can be formed, which is the
basic condition of all metabolic activities. Because proteins in cells cannot exist
independently and must interact with other proteins to achieve biological functions,
protein interactions regulate most biological processes at the cellular level, such as DNA
replication and transfer, signaling, and cell cycle regulation. In order to easily and quickly
discover complexes from protein interaction networks, some scholars proposed to use
graph representation, protein interaction network, protein belongs to the vertex, the
interaction between proteins belongs to the edge, the use of a variety of graph clustering
algorithms, intelligent optimization algorithms and complex network theory for mining
analysis, not only can better understand the topological structure of protein networks, It
can also clarify the biological significance of the complex, which will eventually help
predict unknown protein functions and human disease genes in the new era [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ].
      </p>
      <p>In the 21st century, some scholars first proposed topological structures found in
networks. Complex recognition has attracted extensive attention in the fields of data
mining, bioinformatics and complex networks. They are connected together in a relatively
close way to accomplish specific functions together. It has been found that in the protein
network, the complex has strong biological unity, and the functional similarity of the
proteins contained in the complex exceeds the functional similarity of other protein pairs
in the network. Some scholars have also proved that the density inside the complex is
relatively high, which is related to the biological unity, so it is of great significance to study
the complex recognition algorithm in the biological network. Current scholars have
proposed a cluster-based protein complex discovery method, which uses points or clusters
as seed nodes to expand, regards density as distance targets, and identifies the cluster as a
protein complex when the density value of the cluster is higher than a certain threshold.
Some scholars have proposed an intelligent optimization algorithm represented by
heuristics, which has gradually formed a competitive complex discovery method in
practice. Compared with clustering algorithm, it is mainly used to solve the problem of
social structure discovery in complex networks such as social networks. For example, in
2007, some scholars used genetic algorithm for community mining for the first time, and
proposed a single-path crossover operation suitable for string coding. In order to solve the
insufficient application of faction filtering algorithm (DPM), some scholars introduced the
protein complex scale of distance constraint recognition, and proposed the protein
complex recognition algorithm DPM-DR based on group penetration and distance
constraint, which is more accurate and effective in practice and more comprehensive in
content [2.3]. This is also the beginning of the application of multi-objective evolutionary
programming ideas in protein interaction networks. According to the existing research
results, the most common compound discovery algorithm of protein interaction network
is still clustering algorithm, but there are still many challenges in practical application
research. Therefore, this project mainly discusses the complex discovery method in
protein interaction network from the perspective of food science and technology research
in China, taking the protein interaction network of Saccharomyces cerevisiae as an
example [4].</p>
      <sec id="sec-1-1">
        <title>1.1 Research status of protein complex</title>
        <p>The recognition of protein complex is a hot topic in bioinformatics. The accurate
recognition of protein complex can help human understand the process of living organism.
With the advancement of traditional biological experiments, researchers have obtained a
large amount of PPI data, which provides a basis for the identification of unknown protein
complexes. Based on this, many methods for protein complex identification based on PPI
data have emerged. In this paper, some representative methods for predicting protein
complexes are selected, and these domestic and foreign research methods are summarized
in this section. At present, there are four traditional methods to identify protein complexes
in biological experiments: mass spectrometry, protein microarray, X-ray crystallography
and nuclear magnetic resonance. Although the traditional prediction method has certain
advantages, such as high accuracy, can identify the three-dimensional structure of the
protein complex, can observe the atomic level of detail, but the high cost of the experiment,
long cycle and other disadvantages pose challenges to the implementation of the
experiment. Protein microarray technology requires expensive reactants and reagents;
The method of identifying protein complex based on X-ray crystallography requires high
quality crystal as the experimental medium, and there may be some radiation damage
during the experiment. NMR, on the other hand, may be disturbed by low-quality signals
and may produce spectral overlap. To avoid these problems, the identification of protein
complex [5] by PPIN became a "parallel" to traditional prediction methods. Compared with
the above six methods, other protein complex recognition algorithms are less used. The
typical ones are RSGNM method, which constructs PPIN through Poisson distribution and
defines a series of parameters, and determines whether a protein belongs to protein
complex by adjusting the parameters. The SGNMF method combines the Laplace operator
of PPIN and the Kullback-Lcibler divergence to find protein complexes . In addition,
influenced by heuristic algorithms, some swarm intelligence optimization algorithms are
also used to identify protein complexes. F-MCL method combines Markov method and
Firefly FA method to mine protein complex. ICSC is an improved cuckoo search clustering
algorithm similar to F-MCL method, which is used to detect protein complex in weighted
dynamic PPIN. In ICSC, a dynamic PPIN needs to be constructed first. Then the complex
core structure of the subnetwork is found, and the accessory structure of the protein
complex is obtained by clustering, so as to identify the protein complex. Unlike ICSC, MNC
uses a multi-network model to mine protein complexes, the authors argue that traditional
graph clustering algorithms only identify protein complexes by a single network, ignoring
information from many other networks, while multi-network clustering models mine
protein complexes by relationships between domain interactions. At present, the
mainstream key protein recognition algorithms can be divided into the following five
categories:
1. Methods based on biological experiments</p>
        <p>The most direct methods for identifying key proteins in biology-based experiments are
conditional gene knockout, single gene knockout and RNA interference. Among them, gene
knockout is a molecular biological technique that emerged after the 1980s. Based on the
basic principle of DNA homologous recombination, gene knockout is realized by replacing
the target gene fragment with the homologous fragment of gene. The principle of RNA
interference to identify key proteins is that RNA induces rapid and specific degradation of
homologous mRNA during evolution. Although the traditional method of identifying key
proteins has high accuracy, it requires a lot of human, material and biological resources.
With the development of high-throughput technology and the increasing amount of
biological data, how to efficiently mine key proteins in massive PPins has become a
research hotspot [6].</p>
        <sec id="sec-1-1-1">
          <title>2. Method based on topology structure</title>
          <p>Studies have shown that whether a protein is a key protein is related to the topological
characteristics of protein nodes in PPIN. The method of identifying key proteins based on
topology first needs to calculate the topological centrality of the protein nodes in the
network. The larger the topology centrality value of nodes in the network, the higher the
probability of node becoming a key protein. The "center-lethal" rule proposed by Jeong et
al. shows that in PPIN, the greater the degree value of a node, the more important it is. A
few years later, researchers used degree centrality (DC) to identify key proteins, with
promising results. Since then, there have been many methods to identify key proteins by
using topological centrality. Among them, the intermediate centrality (BC) is obtained by
using the number of shortest paths passed by the node when calculating the topological
centrality of a node. The information centrality (IC) calculates the length of the harmonic
mean path to obtain the topological centrality value of the protein nodes in the network.
Proximity centrality (CC) is to obtain the degree of intimacy between protein nodes and
calculate the topological centrality of nodes. Subgraph centrality (SC) The number of
simple paths taken by a node is calculated to determine topological centrality. Wang et al.
proposed domain centrality (NC) based on edge aggregation coefficient to identify key
proteins in 2011; In addition, eigenvector centrality (EC) and local mean junction
centrality (LAC) are also used to identify key proteins. It is worth mentioning that
Cytoscape is a software for biological network analysis and node centrality evaluation,
making it easier to identify key proteins based on topological centrality. Although the
identification of key proteins based on topological centrality is very accurate, the
identification of key proteins will be greatly affected due to the large number of false
positive data in the protein interaction data used [7].</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>2.Method</title>
      <sec id="sec-2-1">
        <title>2.1 Basic Concepts</title>
        <p>The protein interaction network can be viewed as a simple undirected graph, where node
binding represents a collection of proteins and edits represent interaction binding
between proteins. In this paper, the overlap score evaluation is used to measure the
similarity between subgraphs. If subgraphs have more common nodes, the corresponding
overlap score will be higher and higher. As one of the more common intelligent algorithms,
genetic algorithm is a concept proposed by referring to biological genetic mechanism to
find an optimal solution. The actual process is shown in Figure 1 below: [8.9]</p>
      </sec>
      <sec id="sec-2-2">
        <title>2.2 Protein complex recognition algorithm based on genetic algorithm</title>
        <p>The complex identification analysis is carried out in the protein interaction network, that
is, the graph clustering of the corresponding network, and finally a cluster corresponding
to a protein complex is obtained. In essence, graph clustering refers to a NP-hard
combinatorial optimization method, which uses heuristic search method to obtain
satisfactory results within a specified time, and the selection of seed nodes and cluster
expansion process is the key. Genetic algorithm, as one of the more common algorithms in
current application research, will use population search to select, cross, mutation and
other basic operations on the current population, so as to generate a new generation of
population, and use population evolution to reach or approach the optimal solution. In this
paper, the graph clustering method GAGC with genetic algorithm as the core is used for
complex discovery. The specific steps are as follows: [10.11]</p>
        <p>First, objective function - individual fitness. As an important index of genetic algorithm,
fitness is mainly used to evaluate the degree of superiority and inferiority of individuals in
the population. The actual function value will affect the survival probability of each
individual in the population, and will affect the performance and convergence speed of the
algorithm. The algorithm studied in this paper takes F-measure as an individual fitness
evaluation function, which includes two indicators: accuracy rate and recall rate. The
former refers to the ratio between the compound number correctly identified by the
algorithm and the compound number obtained by the algorithm, while the latter refers to
the accuracy rate of identifying protein complexes in the standard database.</p>
        <p>Second, the initial population generation process. In the research process, factor model
algorithm (IPCA) is used to construct a set of feasible graph structure, which is regarded as
the initial population. The node weights of the network are defined first, and the node with
the greatest weight is selected as the seed node and expanded into clusters. Only the node
with the greatest weight is selected as the seed node for cluster expansion, which cannot
guarantee the diversity of the initial population. Therefore, the IPCA algorithm should be
improved. In the process of selecting seed nodes, the roulette mechanism is added, and the
greater the weight of nodes, the higher the probability of seed nodes. In this way, not only
can the selection of seed nodes be guaranteed to have a greater weight, but also can reflect
the diversity of choices, and finally obtain multiple feasible solutions as the initial
population [12].</p>
        <p>Third, choose a strategy. In order to demonstrate the survival of the fittest concept of
genetic algorithm, high-quality individuals should be allowed to participate in evolution,
and individuals in the population should be selected to produce the next generation of
individuals. At this time, individuals with higher fitness should be selected for
optimization. If the fitness value is selected directly according to the order from high to
low, the diversity of the population will be reduced, and the genetic algorithm will be
premature. Therefore, in the algorithm research, roulette is used to select the probability
of becoming the next generation of individuals in direct proportion to the fitness of nodes.
At the same time, in order to ensure that there are optimal individuals in each generation
of population, if the fitness value of the optimal individual is lower than that of the
previous generation of optimal individuals after a new population for next generation
optimization is generated, So you replace the worst of the current population with the best
of the previous generation.</p>
        <p>Fourth, the crossover strategy. This step is the key content of genetic algorithm. If two
chromosomes are directly selected to cross, there will be a large number of nodes without
cluster belonging, which directly affects the clustering effect. In order to cross effectively,
the genes in the two chromosomes are aligned according to the overlap score, so that the
subgraph represented by the two alleles has more duplicate nodes. In this process, based
on allelic cross operation, the connectivity of new subgraphs generated after gene cross
can be ensured [13].</p>
        <p>Fifth, the strategy of variation. In addition to inheriting the information of the parent's
individual, the offspring produced by cross operation will also vary according to a certain
probability, which fully reflects the diversity of biological heredity. In the process of
mutation, a random mutation is first generated, corresponding to the gene on the
chromosome [14].</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>3. Result analysis</title>
      <sec id="sec-3-1">
        <title>3.1 Experimental design</title>
        <p>In order to verify the application performance of the proposed algorithm, from the
perspective of food science and technology in China, the yeast protein interaction network
data was taken as the research object, and after obtaining the data set meeting the
research requirements, the experimental analysis was carried out according to the process
shown in Figure 2 below:</p>
        <p>Protein Protein Network interaction Average Key protein Cluster
network Number of Active edge number degree Qualitative coefficient
vertices quantity
MIPS 4 546 12 319 5.42 1 016 0.0879
DIP 5 093 24 743 9.72 1 167 0.0973
In order to further explore the accuracy and effectiveness of the applied algorithm, the
ranking results of corresponding protein nodes should be obtained after the node weights
assigned by the descending order algorithm, and protein nodes of different sizes should be
selected as alternative key proteins for comparison and analysis with standard key protein
data. It is possible to specify the number of candidate key proteins that are truly
recognized as key proteins.</p>
      </sec>
      <sec id="sec-3-2">
        <title>3.2 Experimental Results</title>
        <p>In the parameter setting and selection of the algorithm, experiments are conducted
according to the above selected network set, the obtained node weights are processed
according to the sorting-screening method, and the first 100, 200, 300, 400, 500 and 600
nodes in the sequence are selected as alternative key proteins. Thus, the number of true
key proteins contained in the candidate key proteins can be determined, and finally the
results shown in Table 2 below can be obtained:</p>
        <sec id="sec-3-2-1">
          <title>Parameter selection and comparison results</title>
        </sec>
        <sec id="sec-3-2-2">
          <title>MIPS network</title>
          <p>DIP network
100 200 300
500 600 100 200
400 500 600
82
97
105
118
126
127
127
123
130
147
163
172
180
186
400
163
178
186
199
209
226
234
213
222
230
239
249
265
279
255
267
275
278
288
298
312
46
69
77
83
82
81
79
82
103
132
145
145
149
147
300
115
144
181
193
199
203
207
158
186
217
241
253
257
259
201
236
260
283
300
305
302
252
278
301
324
349
349
347
a
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
48
52
61
66
65
67
67
68
68
131 187 238 281 320 75
134 186 234 284 327 79
147 208 260 304 352
149 208 256 308 351
0.9 67 133 184 229 279 331 75 149 209 262 305 349
After defining the algorithm flow, compared with the application performance of other
algorithms, including DC, BC, EC, SC, LAC, NC, and UC, the final results show that the
sensitivity, specificity, positive and negative prediction values of the proposed algorithm
MIPS
DIP</p>
          <p>DC
BC
EC
SC
LAC
NC
UC
EIC
DC
BC
EC
SC
LAC
NC
UC</p>
          <p>SN
are significantly better than those of other algorithms, as shown in Table 3 below. In the
future research and development of food science and technology, scholars should continue
to combine other biological information, machine learning and deep learning algorithms to
comprehensively improve the recognition efficiency and quality of key proteins, in order
to provide a reference for the application of technical algorithms.
Performance comparison results of different algorithms</p>
          <p>Numeric set
method</p>
          <p>EIC 0.440 0.862 0.509 0.826 0.472 0.759</p>
          <p>In this paper, protein networks are divided into 11 groups according to subcellular
localization information. According to the above conclusions, we conclude that the
distribution of key proteins in the organism is not uniform, and the number of key
proteins is more in some regions. We expect to improve the recognition of complexes and,
more importantly, key proteins by clustering protein networks by subcellular location.</p>
          <p>In order to prove the effectiveness of Ess-LGS method, this section selects a variety of
methods to compare ACC, Precision, Recall and F1 values, and compares the performance
of different algorithms on the same data set. Table 4 shows the clustering effect of protein
complexes in 11 subcellular locations in this paper.</p>
          <p>SP</p>
        </sec>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>4. Conclusion</title>
      <p>To sum up, in the face of higher requirements for food safety and biomedicine in the new
era, with the continuous improvement of relevant technical theories, the development of
industry technology is facing new opportunities and challenges. Especially for the
identification of key proteins, although scholars from various countries have proposed and
applied a large number of methods to predict key proteins, how to improve the accuracy of
recognition has been the main problem puzzling scholars. In this paper, a protein complex
recognition method based on genetic algorithm is proposed, and its performance is
obviously better than other algorithms, so it is worth popularizing and applying in clinical
field.
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