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This research was funded by Ministerio de Economia, industria y Competitividad (Spain) grant number SAF2017-88771-R; Ministerio Ciencia e Innovacion (MCIN/AEI/10.13039/501100011033 "ERDF A way of making Europe", Spain) grant number PID2020-118821RB-I00 and Consejeria de Ciencia, Universidades e Innovacion de la CAM (Madrid, Spain) grant number IND2019/BMD-17134.
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Sanchez-Gonzalez, LuciaAuthorFormal Meta-Analysis of Hypoxic Gene Expression Profiles Reveals a Universal Gene Signature
Publicated to:Biomedicines. 10 (9): 2229- - 2022-09-01 10(9), DOI: 10.3390/biomedicines10092229
Authors: Puente-Santamaria, Laura; Sanchez-Gonzalez, Lucia; Pescador, Nuria; Martinez-Costa, Oscar; Ramos-Ruiz, Ricardo; del Peso, Luis
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Abstract
Integrating transcriptional profiles results in identifying gene expression signatures that are more robust than those obtained for individual datasets. However, a direct comparison of datasets derived from heterogeneous experimental conditions is problematic, hence their integration requires applying of specific meta-analysis techniques. The transcriptional response to hypoxia has been the focus of intense research due to its central role in tissue homeostasis and prevalent diseases. Accordingly, many studies have determined the gene expression profile of hypoxic cells. Yet, despite this wealth of information, little effort has been made to integrate these datasets to produce a robust hypoxic signature. We applied a formal meta-analysis procedure to datasets comprising 430 RNA-seq samples from 43 individual studies including 34 different cell types, to derive a pooled estimate of the effect of hypoxia on gene expression in human cell lines grown ingin vitro. This approach revealed that a large proportion of the transcriptome is significantly regulated by hypoxia (8556 out of 20,888 genes identified across studies). However, only a small fraction of the differentially expressed genes (1265 genes, 15%) show an effect size that, according to comparisons to gene pathways known to be regulated by hypoxia, is likely to be biologically relevant. By focusing on genes ubiquitously expressed, we identified a signature of 291 genes robustly and consistently regulated by hypoxia. Overall, we have developed a robust gene signature that characterizes the transcriptomic response of human cell lines exposed to hypoxia in vitro by applying a formal meta-analysis to gene expression profiles.
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Bibliometric impact. Analysis of the contribution and dissemination channel
The work has been published in the journal Biomedicines due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 68/278, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.
From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.82, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)
Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-23, the following number of citations:
- WoS: 2
- Google Scholar: 8