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The impact of incomplete knowledge on evaluation: an experimental benchmark for protein function prediction
Curtis Huttenhower1, Matthew A Hibbs, Chad L Myers
1Department of Computer Science, Princeton University, Princeton, NJ 08540-5233, USA.
Creating a reliable protein function gold standard is crucial for accurate machine learning. This study developed a yeast mitochondria benchmark, revealing that incomplete annotations hinder reliable performance evaluation of computational methods.
Area of Science:
- Genomics
- Computational Biology
- Biochemistry
Background:
- Genomic data expansion necessitates robust protein function prediction and biological network inference.
- Supervised machine learning requires a reliable gold standard for protein function assessment.
- Incomplete gene annotations in model organisms challenge the biological reliability of performance evaluations.
Purpose of the Study:
- To construct and analyze an experimentally validated gold standard for protein function prediction.
- To assess the impact of incomplete functional annotations on machine learning performance evaluation.
- To provide a benchmark for yeast mitochondria to improve future comparative analyses.
Main Methods:
- Comprehensive validation of protein function predictions for mitochondrion biogenesis in Saccharomyces cerevisiae.
- Construction and analysis of an experimentally based gold standard.
- Evaluation of machine learning generalization from incomplete data.
Main Results:
- Machine learning methods can generalize and predict novel biology even with incomplete gold standards.
- Incomplete functional annotations negatively impact the evaluation of machine learning performance.
- Computational approaches performed better than anticipated with sparse data, but relative comparisons are problematic.
Conclusions:
- Incomplete knowledge leads to underestimated method performance and misleading evaluations.
- A benchmark gold standard for yeast mitochondria is provided to mitigate these effects.
- Accurate evaluation of protein function prediction requires a high-quality, experimentally validated gold standard.
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