Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma

Our plain-English summary of Data-driven information retrieval in heterogeneous collections of transcriptomics data links SIM2s to malignant pleural mesothelioma, by J. Caldas, N. Gehlenborg, E. Kettunen, et al (Bioinformatics, 2012).

The study

• Authors: J. Caldas, N. Gehlenborg, E. Kettunen, A. Faisal, M. Rönty, A.G. Nicholson, S. Knuutila, A. Brazma, S. Kaski
• Journal: Bioinformatics
• Published: 2012;28(2):246-53
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Motivation: Genome-wide measurement of transcript levels is an ubiquitous tool in biomedical research. As experimental data continues to be deposited in public databases, it is becoming important to develop search engines that enable the retrieval of relevant studies given a query study. While retrieval systems based on meta-data already exist, data-driven approaches that retrieve studies based on similarities in the expression data itself have a greater potential of uncovering novel biological insights.

Results: We propose an information retrieval method based on differential expression. Our method deals with arbitrary experimental designs and performs competitively with alternative approaches, while making the search results interpretable in terms of differential expression patterns. We show that our model yields meaningful connections between biological conditions from different studies. Finally, we validate a previously unknown connection between malignant pleural mesothelioma and SIM2s suggested by our method, via real-time polymerase chain reaction in an independent set of mesothelioma samples.

Availability: Supplementary data and source code are available from http://www.ebi.ac.uk/fg/research/rex.

In plain English

This was a computer-science methods paper with a small laboratory test added. The authors built a search method, called REx, that links gene-activity studies by similarities in their data. They applied it to 1092 microarray datasets from the ArrayExpress public database (479 human, 445 mouse, 168 rat), split into 6925 comparisons. When they searched with a comparison of malignant pleural mesothelioma (MPM) against normal pleura, the third closest match was a study that reduced the activity of a gene called SIM2s in colon cancer cells. To test this link, they measured gene activity in tumor tissue from 10 MPM patients diagnosed in the UK (six epithelial, four biphasic). They compared it with normal pleural tissue from one 39-year-old man. SIM2s activity was significantly lower in the MPM samples than in the control (P less than 0.05), and a gene called SNAI2 was significantly higher. The authors concluded that SIM2s may have a relevant role in MPM. The study did not examine asbestos exposure. In the retrieval tests, REx scored on average 99% of the best alternative method's score.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Development and evaluation of a computational information-retrieval method for gene expression (microarray) studies, with a laboratory validation by real-time PCR in tumor samples
• Who was studied: 1092 microarray datasets from the ArrayExpress repository (479 human, 445 mouse, 168 rat), retrieved 26 October 2009. Laboratory validation used tumor tissue from 10 MPM patients diagnosed at Royal Brompton and Harefield NHS Trust, UK (six epithelial, four biphasic). The control was normal pleural tissue from one 39-year-old previously healthy male patient operated at Helsinki University Central Hospital.
• Exposure: Not reported. The article does not study asbestos or any other exposure. It compares gene expression in mesothelioma tumors with normal pleura.
• Main results:
  • When the database was searched with a comparison of MPM versus normal human pleura, the third most relevant result was a study that reduced SIM2s activity (RNAi knockdown) in a human colon carcinoma cell line
  • In the earlier MPM dataset analyzed by the model (Gordon et al., 2005), SIM2s was slightly underexpressed compared with pleural control (fold-change 0.87)
  • In the 10 new MPM tumor samples, SIM2s was significantly underexpressed compared with the pleural control (P less than 0.05)
  • MMP3 and SIM2l were detected in all MPM specimens (except MMP3 in one biphasic sample) but not in the pleural control
  • In the MPM samples, SNAI2 was significantly overexpressed (P less than 0.05). Significant overexpression of MMP14 was not confirmed, but MMP14 levels correlated with MMP2 levels (r = 0.74, P less than 0.05)
  • Retrieval performance scores (NDCG) for REx were on average 99% (SD 0.03) of those of the best-performing alternative, a Spearman's correlation approach
• The authors' conclusion: The authors concluded that their results and existing work indicate SIM2s may have a relevant role in MPM, potentially via the epithelial–mesenchymal transition (EMT) network and estrogen signaling. They also concluded that REx can be used to drive biological discovery.
• Limitations the authors state:
  • Because MMP3 and SIM2l were not expressed in the pleural control, numerical fold-change values could not be obtained for those genes
  • The authors suggest the gene set (GSEA) encoding used by the method may be suboptimal

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma.

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