PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach
Abstract Background Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12859-023-05187-2 |
| _version_ | 1797863361043496960 |
|---|---|
| author | Malik Yousef Fatma Ozdemir Amhar Jaber Jens Allmer Burcu Bakir-Gungor |
| author_facet | Malik Yousef Fatma Ozdemir Amhar Jaber Jens Allmer Burcu Bakir-Gungor |
| author_sort | Malik Yousef |
| collection | DOAJ |
| description | Abstract Background Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases. Results PriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research. Conclusions PriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine. |
| first_indexed | 2024-04-09T22:35:27Z |
| format | Article |
| id | doaj.art-d6cbb6f5475d4e0abe9c2a187a4856e8 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-04-09T22:35:27Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-d6cbb6f5475d4e0abe9c2a187a4856e82023-03-22T12:33:34ZengBMCBMC Bioinformatics1471-21052023-02-0124112410.1186/s12859-023-05187-2PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approachMalik Yousef0Fatma Ozdemir1Amhar Jaber2Jens Allmer3Burcu Bakir-Gungor4Department of Information Systems, Zefat Academic CollegeDepartment of Computer Engineering, Faculty of Engineering, Abdullah Gul UniversityDepartment of Computer Engineering, Faculty of Engineering, Abdullah Gul UniversityMedical Informatics and Bioinformatics, Institute for Measurement Engineering and Sensor Technology, Hochschule Ruhr West, University of Applied SciencesDepartment of Computer Engineering, Faculty of Engineering, Abdullah Gul UniversityAbstract Background Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases. Results PriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research. Conclusions PriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine.https://doi.org/10.1186/s12859-023-05187-2Feature selectionFeature scoringFeature groupingBiological knowledge integrationKEGG pathwayClassification |
| spellingShingle | Malik Yousef Fatma Ozdemir Amhar Jaber Jens Allmer Burcu Bakir-Gungor PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach BMC Bioinformatics Feature selection Feature scoring Feature grouping Biological knowledge integration KEGG pathway Classification |
| title | PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach |
| title_full | PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach |
| title_fullStr | PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach |
| title_full_unstemmed | PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach |
| title_short | PriPath: identifying dysregulated pathways from differential gene expression via grouping, scoring, and modeling with an embedded feature selection approach |
| title_sort | pripath identifying dysregulated pathways from differential gene expression via grouping scoring and modeling with an embedded feature selection approach |
| topic | Feature selection Feature scoring Feature grouping Biological knowledge integration KEGG pathway Classification |
| url | https://doi.org/10.1186/s12859-023-05187-2 |
| work_keys_str_mv | AT malikyousef pripathidentifyingdysregulatedpathwaysfromdifferentialgeneexpressionviagroupingscoringandmodelingwithanembeddedfeatureselectionapproach AT fatmaozdemir pripathidentifyingdysregulatedpathwaysfromdifferentialgeneexpressionviagroupingscoringandmodelingwithanembeddedfeatureselectionapproach AT amharjaber pripathidentifyingdysregulatedpathwaysfromdifferentialgeneexpressionviagroupingscoringandmodelingwithanembeddedfeatureselectionapproach AT jensallmer pripathidentifyingdysregulatedpathwaysfromdifferentialgeneexpressionviagroupingscoringandmodelingwithanembeddedfeatureselectionapproach AT burcubakirgungor pripathidentifyingdysregulatedpathwaysfromdifferentialgeneexpressionviagroupingscoringandmodelingwithanembeddedfeatureselectionapproach |