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Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure.

ABSTRACT: Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein structure features. To address this problem, here we introduce an index to quantify the protein-function criticality of a residue based on experimental data and a strategy aimed to optimize both, descriptors of protein structure (physicochemical and centrality descriptors) and machine learning algorithms, to minimize the error in the classification of critical residues. We observed that both physicochemical and centrality descriptors of residues effectively relate protein structure and protein function, and that physicochemical descriptors better describe critical residues. We also show that critical residues are better classified when residue criticality is considered as a binary attribute (i.e., residues are considered critical or not critical). Using this binary annotation for critical residues 8 models rendered accurate and non-overlapping classification of critical residues, confirming the multi-factorial character of the structure-function relationship of proteins.

SUBMITTER: Corral-Corral R

PROVIDER: S-EPMC6151554 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure.

Corral-Corral Ricardo R Beltrán Jesús A JA Brizuela Carlos A CA Del Rio Gabriel G

Molecules (Basel, Switzerland) 20171009 10

Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein ...[more]

PMID: 28991206

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Project description:BackgroundMissing data in electronic health records is inevitable and considered to be nonrandom. Several studies have found that features indicating missing patterns (missingness) encode useful information about a patient's health and advocate for their inclusion in clinical prediction models. But their effectiveness has not been comprehensively evaluated.ObjectiveThe goal of the research is to study the effect of including informative missingness features in machine learning models for various clinically relevant outcomes and explore robustness of these features across patient subgroups and task settings.MethodsA total of 48,336 electronic health records from the 2012 and 2019 PhysioNet Challenges were used, and mortality, length of stay, and sepsis outcomes were chosen. The latter dataset was multicenter, allowing external validation. Gated recurrent units were used to learn sequential patterns in the data and classify or predict labels of interest. Models were evaluated on various criteria and across population subgroups evaluating discriminative ability and calibration.ResultsGenerally improved model performance in retrospective tasks was observed on including missingness features. Extent of improvement depended on the outcome of interest (area under the curve of the receiver operating characteristic [AUROC] improved from 1.2% to 7.7%) and even patient subgroup. However, missingness features did not display utility in a simulated prospective setting, being outperformed (0.9% difference in AUROC) by the model relying only on pathological features. This was despite leading to earlier detection of disease (true positives), since including these features led to a concomitant rise in false positive detections.ConclusionsThis study comprehensively evaluated effectiveness of missingness features on machine learning models. A detailed understanding of how these features affect model performance may lead to their informed use in clinical settings especially for administrative tasks like length of stay prediction where they present the greatest benefit. While missingness features, representative of health care processes, vary greatly due to intra- and interhospital factors, they may still be used in prediction models for clinically relevant outcomes. However, their use in prospective models producing frequent predictions needs to be explored further.

Dataset Information

Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure.

Publications

Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure.

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