# 生物网络

A biological network is any network that applies to biological systems. A network is any system with sub-units that are linked into a whole, such as species units linked into a whole food web. Biological networks provide a mathematical representation of connections found in ecological, evolutionary, and physiological studies, such as neural networks.[1] The analysis of biological networks with respect to human diseases has led to the field of network medicine.[2][3]

A biological network is any network that applies to biological systems. A network is any system with sub-units that are linked into a whole, such as species units linked into a whole food web. Biological networks provide a mathematical representation of connections found in ecological, evolutionary, and physiological studies, such as neural networks. The analysis of biological networks with respect to human diseases has led to the field of network medicine.

## Network biology and bioinformatics

Complex biological systems may be represented and analyzed as computable networks. For example, ecosystems can be modeled as networks of interacting species or a protein can be modeled as a network of amino acids. Breaking a protein down farther, amino acids can be represented as a network of connected atoms, such as carbon, nitrogen, and oxygen. Nodes and edges are the basic components of a network. Nodes represent units in the network, while edges represent the interactions between the units. Nodes can represent a wide array of biological units, from individual organisms to individual neurons in the brain. Two important properties of a network are degree and betweenness centrality. Degree (or connectivity, a distinct usage from that used in graph theory) is the number of edges that connect a node, while betweenness is a measure of how central a node is in a network.[6] Nodes with high betweenness essentially serve as bridges between different portions of the network (i.e. interactions must pass through this node to reach other portions of the network). In social networks, nodes with high degree or high betweenness may play important roles in the overall composition of a network.

Complex biological systems may be represented and analyzed as computable networks. For example, ecosystems can be modeled as networks of interacting species or a protein can be modeled as a network of amino acids. Breaking a protein down farther, amino acids can be represented as a network of connected atoms, such as carbon, nitrogen, and oxygen. Nodes and edges are the basic components of a network. Nodes represent units in the network, while edges represent the interactions between the units. Nodes can represent a wide array of biological units, from individual organisms to individual neurons in the brain. Two important properties of a network are degree and betweenness centrality. Degree (or connectivity, a distinct usage from that used in graph theory) is the number of edges that connect a node, while betweenness is a measure of how central a node is in a network. Nodes with high betweenness essentially serve as bridges between different portions of the network (i.e. interactions must pass through this node to reach other portions of the network). In social networks, nodes with high degree or high betweenness may play important roles in the overall composition of a network.

As early as the 1980s, researchers started viewing DNA or genomes as the dynamic storage of a language system with precise computable finite states represented as a finite state machine.[7] Recent complex systems research has also suggested some far-reaching commonality in the organization of information in problems from biology, computer science, and physics, such as the Bose–Einstein condensate (a special state of matter).[8]

As early as the 1980s, researchers started viewing DNA or genomes as the dynamic storage of a language system with precise computable finite states represented as a finite state machine. Recent complex systems research has also suggested some far-reaching commonality in the organization of information in problems from biology, computer science, and physics, such as the Bose–Einstein condensate (a special state of matter).

Bioinformatics has increasingly shifted its focus from individual genes, proteins, and search algorithms to large-scale networks often denoted as -omes such as biome, interactome, genome and proteome. Such theoretical studies have revealed that biological networks share many features with other networks such as the Internet or social networks, e.g. their network topology.

Bioinformatics has increasingly shifted its focus from individual genes, proteins, and search algorithms to large-scale networks often denoted as -omes such as biome, interactome, genome and proteome. Such theoretical studies have revealed that biological networks share many features with other networks such as the Internet or social networks, e.g. their network topology.

## Networks in biology

### Protein–protein interaction networks

Many protein–protein interactions (PPIs) in a cell form protein interaction networks (PINs) where proteins are nodes and their interactions are edges.[11] PINs are the most intensely analyzed networks in biology. There are dozens of PPI detection methods to identify such interactions. The yeast two-hybrid system is a commonly used experimental technique for the study of binary interactions.[12]

Many protein–protein interactions (PPIs) in a cell form protein interaction networks (PINs) where proteins are nodes and their interactions are edges. PINs are the most intensely analyzed networks in biology. There are dozens of PPI detection methods to identify such interactions. The yeast two-hybrid system is a commonly used experimental technique for the study of binary interactions.

Recent studies have indicated conservation of molecular networks through deep evolutionary time.[15] Moreover, it has been discovered that proteins with high degrees of connectedness are more likely to be essential for survival than proteins with lesser degrees.[16] This suggests that the overall composition of the network (not simply interactions between protein pairs) is important for the overall functioning of an organism.

Recent studies have indicated conservation of molecular networks through deep evolutionary time. Moreover, it has been discovered that proteins with high degrees of connectedness are more likely to be essential for survival than proteins with lesser degrees. This suggests that the overall composition of the network (not simply interactions between protein pairs) is important for the overall functioning of an organism.

### Gene regulatory networks (DNA–protein interaction networks)

The activity of genes is regulated by transcription factors, proteins that typically bind to DNA. Most transcription factors bind to multiple binding sites in a genome. As a result, all cells have complex gene regulatory networks. For instance, the human genome encodes on the order of 1,400 DNA-binding transcription factors that regulate the expression of more than 20,000 human genes.[19] Technologies to study gene regulatory networks include ChIP-chip, ChIP-seq, CliP-seq, and others.

The activity of genes is regulated by transcription factors, proteins that typically bind to DNA. Most transcription factors bind to multiple binding sites in a genome. As a result, all cells have complex gene regulatory networks. For instance, the human genome encodes on the order of 1,400 DNA-binding transcription factors that regulate the expression of more than 20,000 human genes. Technologies to study gene regulatory networks include ChIP-chip, ChIP-seq, CliP-seq, and others.

### Gene co-expression networks (transcript–transcript association networks)

--～～～Gene co-expression networks  基因共表达网络

Gene co-expression networks can be interpreted as association networks between variables that measure transcript abundances. These networks have been used to provide a systems biologic analysis of DNA microarray data, RNA-seq data, miRNA data etc.

Gene co-expression networks can be interpreted as association networks between variables that measure transcript abundances. These networks have been used to provide a systems biologic analysis of DNA microarray data, RNA-seq data, miRNA data etc.

weighted gene co-expression network analysis is widely used to identify co-expression modules and intramodular hub genes. Co-expression modules may correspond to cell types or pathways. Highly connected intramodular hubs can be interpreted as representatives of their respective module.

weighted gene co-expression network analysis is widely used to identify co-expression modules and intramodular hub genes. Co-expression modules may correspond to cell types or pathways. Highly connected intramodular hubs can be interpreted as representatives of their respective module.

### Metabolic networks

The chemical compounds of a living cell are connected by biochemical reactions which convert one compound into another. The reactions are catalyzed by enzymes. Thus, all compounds in a cell are parts of an intricate biochemical network of reactions which is called metabolic network. It is possible to use network analyses to infer how selection acts on metabolic pathways.[6]

The chemical compounds of a living cell are connected by biochemical reactions which convert one compound into another. The reactions are catalyzed by enzymes. Thus, all compounds in a cell are parts of an intricate biochemical network of reactions which is called metabolic network. It is possible to use network analyses to infer how selection acts on metabolic pathways.

### Signaling networks

Signals are transduced within cells or in between cells and thus form complex signaling networks. For instance, in the MAPK/ERK pathway is transduced from the cell surface to the cell nucleus by a series of protein–protein interactions, phosphorylation reactions, and other events. Signaling networks typically integrate protein–protein interaction networks, gene regulatory networks, and metabolic networks.

Signals are transduced within cells or in between cells and thus form complex signaling networks. For instance, in the MAPK/ERK pathway is transduced from the cell surface to the cell nucleus by a series of protein–protein interactions, phosphorylation reactions, and other events. Signaling networks typically integrate protein–protein interaction networks, gene regulatory networks, and metabolic networks.

### Neuronal networks

The complex interactions in the brain make it a perfect candidate to apply network theory. Neurons in the brain are deeply connected with one another and this results in complex networks being present in the structural and functional aspects of the brain.[20] For instance, small-world network properties have been demonstrated in connections between cortical areas of the primate brain[21] or during swallowing in humans.[22] This suggests that cortical areas of the brain are not directly interacting with each other, but most areas can be reached from all others through only a few interactions.

The complex interactions in the brain make it a perfect candidate to apply network theory. Neurons in the brain are deeply connected with one another and this results in complex networks being present in the structural and functional aspects of the brain. For instance, small-world network properties have been demonstrated in connections between cortical areas of the primate brain or during swallowing in humans. This suggests that cortical areas of the brain are not directly interacting with each other, but most areas can be reached from all others through only a few interactions.

### Food webs

All organisms are connected to each other through feeding interactions. That is, if a species eats or is eaten by another species, they are connected in an intricate food web of predator and prey interactions. The stability of these interactions has been a long-standing question in ecology.[26] That is to say, if certain individuals are removed, what happens to the network (i.e. does it collapse or adapt)? Network analysis can be used to explore food web stability and determine if certain network properties result in more stable networks. Moreover, network analysis can be used to determine how selective removals of species will influence the food web as a whole.[27] This is especially important considering the potential species loss due to global climate change.

All organisms are connected to each other through feeding interactions. That is, if a species eats or is eaten by another species, they are connected in an intricate food web of predator and prey interactions. The stability of these interactions has been a long-standing question in ecology. That is to say, if certain individuals are removed, what happens to the network (i.e. does it collapse or adapt)? Network analysis can be used to explore food web stability and determine if certain network properties result in more stable networks. Moreover, network analysis can be used to determine how selective removals of species will influence the food web as a whole. This is especially important considering the potential species loss due to global climate change.

### Between-species interaction networks

In biology, pairwise interactions have historically been the focus of intense study. With the recent advances in network science, it has become possible to scale up pairwise interactions to include individuals of many species involved in many sets of interactions to understand the structure and function of larger ecological networks.[30] The use of network analysis can allow for both the discovery and understanding how these complex interactions link together within the system’s network, a property which has previously been overlooked. This powerful tool allows for the study of various types of interactions (from competitive to cooperative) using the same general framework.[31] For example, plant-pollinator interactions are mutually beneficial and often involve many different species of pollinators as well as many different species of plants. These interactions are critical to plant reproduction and thus the accumulation of resources at the base of the food chain for primary consumers, yet these interaction networks are threatened by anthropogenic change. The use of network analysis can illuminate how pollination networks work and may in turn inform conservation efforts.[32] Within pollination networks, nestedness (i.e., specialists interact with a subset of species that generalists interact with), redundancy (i.e., most plants are pollinated by many pollinators), and modularity play a large role in network stability.[32][33] These network properties may actually work to slow the spread of disturbance effects through the system and potentially buffer the pollination network from anthropogenic changes somewhat.[33] More generally, the structure of species interactions within an ecological network can tell us something about the diversity, richness, and robustness of the network.[34] Researchers can even compare current constructions of species interactions networks with historical reconstructions of ancient networks to determine how networks have changed over time.[35] Recent research into these complex species interactions networks is highly concerned with understanding what factors (e.g., diversity) lead to network stability.[36]

In biology, pairwise interactions have historically been the focus of intense study. With the recent advances in network science, it has become possible to scale up pairwise interactions to include individuals of many species involved in many sets of interactions to understand the structure and function of larger ecological networks. The use of network analysis can allow for both the discovery and understanding how these complex interactions link together within the system’s network, a property which has previously been overlooked. This powerful tool allows for the study of various types of interactions (from competitive to cooperative) using the same general framework. For example, plant-pollinator interactions are mutually beneficial and often involve many different species of pollinators as well as many different species of plants. These interactions are critical to plant reproduction and thus the accumulation of resources at the base of the food chain for primary consumers, yet these interaction networks are threatened by anthropogenic change. The use of network analysis can illuminate how pollination networks work and may in turn inform conservation efforts. Within pollination networks, nestedness (i.e., specialists interact with a subset of species that generalists interact with), redundancy (i.e., most plants are pollinated by many pollinators), and modularity play a large role in network stability. These network properties may actually work to slow the spread of disturbance effects through the system and potentially buffer the pollination network from anthropogenic changes somewhat. Researchers can even compare current constructions of species interactions networks with historical reconstructions of ancient networks to determine how networks have changed over time. Recent research into these complex species interactions networks is highly concerned with understanding what factors (e.g., diversity) lead to network stability.

### Within-species interaction networks

Network analysis provides the ability to quantify associations between individuals, which makes it possible to infer details about the network as a whole at the species and/or population level.[42] One of the most attractive features of the network paradigm would be that it provides a single conceptual framework in which the social organisation of animals at all levels (individual, dyad, group, population) and for all types of interaction (aggressive, cooperative, sexual etc.) can be studied.[43]

Network analysis provides the ability to quantify associations between individuals, which makes it possible to infer details about the network as a whole at the species and/or population level. One of the most attractive features of the network paradigm would be that it provides a single conceptual framework in which the social organisation of animals at all levels (individual, dyad, group, population) and for all types of interaction (aggressive, cooperative, sexual etc.) can be studied.

Researchers interested in ethology across a multitude of taxa, from insects to primates, are starting to incorporate network analysis into their research. Researchers interested in social insects (e.g., ants and bees) have used network analyses to better understand division of labor, task allocation, and foraging optimization within colonies;[46][47][48] Other researchers are interested in how certain network properties at the group and/or population level can explain individual level behaviors. Studies have demonstrated how animal social network structure can be influenced by factors ranging from characteristics of the environment to characteristics of the individual, such as developmental experience and personality. At the level of the individual, the patterning of social connections can be an important determinant of fitness, predicting both survival and reproductive success. At the population level, network structure can influence the patterning of ecological and evolutionary processes, such as frequency-dependent selection and disease and information transmission.[49] For instance, a study on wire-tailed manakins (a small passerine bird) found that a male’s degree in the network largely predicted the ability of the male to rise in the social hierarchy (i.e. eventually obtain a territory and matings).[50] In bottlenose dolphin groups, an individual’s degree and betweenness centrality values may predict whether or not that individual will exhibit certain behaviors, like the use of side flopping and upside-down lobtailing to lead group traveling efforts; individuals with high betweenness values are more connected and can obtain more information, and thus are better suited to lead group travel and therefore tend to exhibit these signaling behaviors more than other group members.[51]

Researchers interested in ethology across a multitude of taxa, from insects to primates, are starting to incorporate network analysis into their research. Researchers interested in social insects (e.g., ants and bees) have used network analyses to better understand division of labor, task allocation, and foraging optimization within colonies; Other researchers are interested in how certain network properties at the group and/or population level can explain individual level behaviors. Studies have demonstrated how animal social network structure can be influenced by factors ranging from characteristics of the environment to characteristics of the individual, such as developmental experience and personality. At the level of the individual, the patterning of social connections can be an important determinant of fitness, predicting both survival and reproductive success. At the population level, network structure can influence the patterning of ecological and evolutionary processes, such as frequency-dependent selection and disease and information transmission. For instance, a study on wire-tailed manakins (a small passerine bird) found that a male’s degree in the network largely predicted the ability of the male to rise in the social hierarchy (i.e. eventually obtain a territory and matings). In bottlenose dolphin groups, an individual’s degree and betweenness centrality values may predict whether or not that individual will exhibit certain behaviors, like the use of side flopping and upside-down lobtailing to lead group traveling efforts; individuals with high betweenness values are more connected and can obtain more information, and thus are better suited to lead group travel and therefore tend to exhibit these signaling behaviors more than other group members.

Social network analysis can also be used to describe the social organization within a species more generally, which frequently reveals important proximate mechanisms promoting the use of certain behavioral strategies. These descriptions are frequently linked to ecological properties (e.g., resource distribution). For example, network analyses revealed subtle differences in the group dynamics of two related equid fission-fusion species, Grevy’s zebra and onagers, living in variable environments; Grevy’s zebras show distinct preferences in their association choices when they fission into smaller groups, whereas onagers do not.[58] Similarly, researchers interested in primates have also utilized network analyses to compare social organizations across the diverse primate order, suggesting that using network measures (such as centrality, assortativity, modularity, and betweenness) may be useful in terms of explaining the types of social behaviors we see within certain groups and not others.[59]

Social network analysis can also be used to describe the social organization within a species more generally, which frequently reveals important proximate mechanisms promoting the use of certain behavioral strategies. These descriptions are frequently linked to ecological properties (e.g., resource distribution). For example, network analyses revealed subtle differences in the group dynamics of two related equid fission-fusion species, Grevy’s zebra and onagers, living in variable environments; Grevy’s zebras show distinct preferences in their association choices when they fission into smaller groups, whereas onagers do not. Similarly, researchers interested in primates have also utilized network analyses to compare social organizations across the diverse primate order, suggesting that using network measures (such as centrality, assortativity, modularity, and betweenness) may be useful in terms of explaining the types of social behaviors we see within certain groups and not others.

Finally, social network analysis can also reveal important fluctuations in animal behaviors across changing environments. For example, network analyses in female chacma baboons (Papio hamadryas ursinus) revealed important dynamic changes across seasons which were previously unknown; instead of creating stable, long-lasting social bonds with friends, baboons were found to exhibit more variable relationships which were dependent on short-term contingencies related to group level dynamics as well as environmental variability.[62] Changes in an individual's social network environment can also influence characteristics such as 'personality': for example, social spiders that huddle with bolder neighbours tend to increase also in boldness.[63] This is a very small set of broad examples of how researchers can use network analysis to study animal behavior. Research in this area is currently expanding very rapidly, especially since the broader development of animal borne tags and computer vision that can be used to automate the collection of social associations.[64] Social network analysis is a valuable tool for studying animal behavior across all animal species, and has the potential to uncover new information about animal behavior and social ecology that was previously poorly understood.

Finally, social network analysis can also reveal important fluctuations in animal behaviors across changing environments. For example, network analyses in female chacma baboons (Papio hamadryas ursinus) revealed important dynamic changes across seasons which were previously unknown; instead of creating stable, long-lasting social bonds with friends, baboons were found to exhibit more variable relationships which were dependent on short-term contingencies related to group level dynamics as well as environmental variability. Changes in an individual's social network environment can also influence characteristics such as 'personality': for example, social spiders that huddle with bolder neighbours tend to increase also in boldness. This is a very small set of broad examples of how researchers can use network analysis to study animal behavior. Research in this area is currently expanding very rapidly, especially since the broader development of animal borne tags and computer vision that can be used to automate the collection of social associations. Social network analysis is a valuable tool for studying animal behavior across all animal species, and has the potential to uncover new information about animal behavior and social ecology that was previously poorly understood.