# The gene network and knowledge base on human thermoregulation

## TL;DR

This paper presents a computer-reconstructed gene network and knowledge base for human thermoregulation, identifying key genes, proteins, and microRNAs involved in maintaining body temperature.

## Contribution

The novel contribution is the creation of the Termo_Reg_Human 1.0 knowledge base, which includes a detailed gene network and prioritization of key regulatory elements in human thermoregulation.

## Key findings

- The human thermoregulation gene network includes 469 genes, 473 proteins, and 265 microRNAs with their interactions.
- Key genes like UCP1, VEGFA, PPARG, and DDIT3 were identified as central to thermoregulation due to their high number of interactions.
- The gene set is enriched with genes that originated early in evolution, including during the divergence of vertebrates.

## Abstract

Reconstruction and analysis of gene networks regulating biological processes are among the modern methodological approaches for studying complex biological systems that ensure the vital activity of organisms. Thermoregulation is an important evolutionary acquisition of warm-blooded animals. Multiple physiological systems (nervous, cardiovascular, endocrine, respiratory, muscular, etc.) are involved in this process, maintaining stable body temperature despite changes in ambient temperature. This study aims to perform a computer reconstruction of the human thermoregulation gene network and present the results in the Termo_Reg_Human 1.0 knowledge base. The gene network was reconstructed using the ANDSystem software and information system, designed for the automated extraction of knowledge and facts from scientific publications and biomedical databases based on machine learning and artificial intelligence methods. The Termo_Reg_Human 1.0 knowledge base (https://www.sysbio.ru/ThermoReg_Human/) contains information about the human thermoregulation gene network, including a description of 469 genes, 473 proteins, and 265 microRNAs important for its functioning, interactions between these objects, and the evolutionary characteristics of the genes. Using the ANDVisio software tool (a module of ANDSystem), each gene, protein, and microRNA involved in the thermoregulation of the human body was prioritized according to its functional significance, i. e., the number of interactions with other objects in the reconstructed gene network. It was found that the key objects with the largest number of functional interactions in the human thermoregulation gene network included the UCP1, VEGFA, PPARG and DDIT3 genes; STAT3, JUN, VEGFA, TLR4 and TNFA proteins; and the microRNAs hsa-mir-335 and hsa-mir-26b. We revealed that the set of 469 human genes from the network was enriched with genes whose ancestral forms originated at an early evolutionary stage (Unicellular organisms, the root of the phylostratigraphic tree) and at the stage of Vertebrata divergence.