# A Comparative Analysis of Gene Expression Profiling by Statistical and Machine Learning Approaches

arXiv: https://arxiv.org/abs/2402.00926 · HTML: https://mlsanity.com/paper/2402.00926/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 63 references that are in the map.
- First posted on arXiv 1 Feb 2024.

## Builds on (most cited first, 13 of 13)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [Convex optimization](https://mlsanity.com/paper/2106.01946/) (2021)
- [Graph Neural Networks: A Review of Methods and Applications](https://mlsanity.com/paper/1812.08434/) (2018)
- [Captum: A unified and generic model interpretability library for PyTorch](https://mlsanity.com/paper/2009.07896/) (2020)
- [Interpretable Machine Learning: Fundamental Principles and 10 Grand Challenges](https://mlsanity.com/paper/2103.11251/) (2021)
- [OpenXAI: Towards a Transparent Evaluation of Model Explanations](https://mlsanity.com/paper/2206.11104/) (2022)
- [Hybrid Approach of Relation Network and Localized Graph Convolutional Filtering for Breast Cancer Subtype Classification](https://mlsanity.com/paper/1711.05859/) (2017)
- [Machine Learning Methods for Cancer Classification Using Gene Expression Data: A Review](https://mlsanity.com/paper/2301.12222/) (2023)

## Abstract (arXiv)

Many machine learning models have been proposed to classify phenotypes from gene expression data. In addition to their good performance, these models can potentially provide some understanding of phenotypes by extracting explanations for their decisions. These explanations often take the form of a list of genes ranked in order of importance for the predictions, the highest-ranked genes being interpreted as linked to the phenotype. We discuss the biological and the methodological limitations of such explanations. Experiments are performed on several datasets gathering cancer and healthy tissue samples from the TCGA, GTEx and TARGET databases. A collection of machine learning models including logistic regression, multilayer perceptron, and graph neural network are trained to classify samples according to their cancer type. Gene rankings are obtained from explainability methods adapted to these models, and compared to the ones from classical statistical feature selection methods such as mutual information, DESeq2, and EdgeR. Interestingly, on simple tasks, we observe that the information learned by black-box neural networks is related to the notion of differential expression. In all cases, a small set containing the best-ranked genes is sufficient to achieve a good classification. However, these genes differ significantly between the methods and similar classification performance can be achieved with numerous lower ranked genes. In conclusion, although these methods enable the identification of biomarkers characteristic of certain pathologies, our results question the completeness of the selected gene sets and thus of explainability by the identification of the underlying biological processes.