Functional network analysis reveals an immune tolerance mechanism in cancer Journal Article
| Authors: | Mathews, J. C.; Nadeem, S.; Pouryahya, M.; Belkhatir, Z.; Deasy, J. O.; Levine, A. J.; Tannenbaum, A. R. |
| Article Title: | Functional network analysis reveals an immune tolerance mechanism in cancer |
| Abstract: | We present a technique to construct a simplification of a feature network which can be used for interactive data exploration, biological hypothesis generation, and the detection of communities or modules of cofunctional features. These are modules of features that are not necessarily correlated, but nevertheless exhibit common function in their network context as measured by similarity of relationships with neighboring features. In the case of genetic networks, traditional pathway analyses tend to assume that, ideally, all genes in a module exhibit very similar function, independent of relationships with other genes. The proposed technique explicitly relaxes this assumption by employing the comparison of relational profiles. For example, two genes which always activate a third gene are grouped together even if they never do so concurrently. They have common, but not identical, function. The comparison is driven by an average of a certain computationally efficient comparison metric between Gaussian mixture models. The method has its basis in the local connection structure of the network and the collection of joint distributions of the data associated with nodal neighborhoods. It is benchmarked on networks with known community structures. As the main application, we analyzed the gene regulatory network in lung adenocarcinoma, finding a cofunctional module of genes including the pregnancy-specific glycoproteins (PSGs). About 20% of patients with lung, breast, uterus, and colon cancer in The Cancer Genome Atlas (TCGA) have an elevated PSG+ signature, with associated poor group prognosis. In conjunction with previous results relating PSGs to tolerance in the immune system, these findings implicate the PSGs in a potential immune tolerance mechanism of cancers. © 2020 National Academy of Sciences. All rights reserved. |
| Keywords: | breast cancer; gene function; cancer genetics; immunological tolerance; immune tolerance; lung adenocarcinoma; colon cancer; gene regulatory network; gaussian mixture model; uterus cancer; statistical model; complex networks; cancer prognosis; data processing; community structure; human; priority journal; article; optimal transport; community detection; gaussian mixture models; pregnancy associated protein |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 117 |
| Issue: | 28 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2020-07-14 |
| Start Page: | 16339 |
| End Page: | 16345 |
| Language: | English |
| DOI: | 10.1073/pnas.2002179117 |
| PUBMED: | 32601217 |
| PROVIDER: | scopus |
| PMCID: | PMC7368249 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
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