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. 2023 Jan 21;12(3):388.
doi: 10.3390/cells12030388.

HGCA2.0: An RNA-Seq Based Webtool for Gene Coexpression Analysis in Homo sapiens

Vasileios L Zogopoulos  1   2 , Apostolos Malatras  3 , Konstantinos Kyriakidis  1   4 , Chrysanthi Charalampous  5 , Evanthia A Makrygianni  6 , Stéphanie Duguez  7 , Marianna A Koutsi  5 , Marialena Pouliou  5 , Christos Vasileiou  1   8 , William J Duddy  7 , Marios Agelopoulos  5 , George P Chrousos  6 , Vassiliki A Iconomidou  2 , Ioannis Michalopoulos  1
Affiliations

HGCA2.0: An RNA-Seq Based Webtool for Gene Coexpression Analysis in Homo sapiens

Vasileios L Zogopoulos et al. Cells. .

Abstract

Genes with similar expression patterns in a set of diverse samples may be considered coexpressed. Human Gene Coexpression Analysis 2.0 (HGCA2.0) is a webtool which studies the global coexpression landscape of human genes. The website is based on the hierarchical clustering of 55,431 Homo sapiens genes based on a large-scale coexpression analysis of 3500 GTEx bulk RNA-Seq samples of healthy individuals, which were selected as the best representative samples of each tissue type. HGCA2.0 presents subclades of coexpressed genes to a gene of interest, and performs various built-in gene term enrichment analyses on the coexpressed genes, including gene ontologies, biological pathways, protein families, and diseases, while also being unique in revealing enriched transcription factors driving coexpression. HGCA2.0 has been successful in identifying not only genes with ubiquitous expression patterns, but also tissue-specific genes. Benchmarking showed that HGCA2.0 belongs to the top performing coexpression webtools, as shown by STRING analysis. HGCA2.0 creates working hypotheses for the discovery of gene partners or common biological processes that can be experimentally validated. It offers a simple and intuitive website design and user interface, as well as an API endpoint.

Keywords: RNA-Seq; bioinformatics; co-expression; gene coexpression analysis; gene coexpression network; transcriptomics; webtool.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The five branching points (depicted as numbered dots), from the driver gene leaf (GNG4) until the root of the clade, constitute the internal nodes of this coexpression clade.
Figure 2
Figure 2
RPL11 14 internal node HGCA2.0 coexpression clade.
Figure 3
Figure 3
HGCA2.0 MT1M 5 internal node coexpression clade.
Figure 4
Figure 4
HGCA2.0 HLA-DMA coexpression clade. The 7 internal node clade is included in the green box, while the expanded 14 internal node clade is included in the red box.
Figure 5
Figure 5
HGCA2.0 NLRC5 6 internal node coexpression clade.
Figure 6
Figure 6
HGCA2.0 STAT1 5 internal node coexpression clade.
Figure 7
Figure 7
HGCA2.0 TMPRSS2 6 internal node coexpression clade.
Figure 8
Figure 8
HGCA2.0 C1orf68 5 internal node coexpression clade.
Figure 9
Figure 9
Phylogenetic tree resulting from MUSCLE multiple sequence alignment of the protein sequences of the genes of the HGCA2.0 C1orf68 (XP32) coexpression clade, as viewed by Dendroscope [91].
Figure 10
Figure 10
HGCA2.0 HSP90AA1 14 internal node coexpression clade.
Figure 11
Figure 11
HGCA2.0 HSP90B1 5 internal node coexpression clade.
Figure 12
Figure 12
HGCA2.0 NRP1 5 internal node coexpression clade.
Figure 13
Figure 13
HGCA2.0 NR3C1 3 internal node coexpression clade.
Figure 14
Figure 14
HGCA2.0 CSHL1 12 internal node coexpression clade.
Figure 15
Figure 15
HGCA2.0 coexpression clades of sense genes and their respective antisenses; (a) HGCA2.0 GATA3 2 internal node coexpression clade; (b) HGCA2.0 NR2F1 3 internal node coexpression clade; (c) HGCA2.0 MEF2C 2 internal node coexpression clade.
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