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Interpreting machine learning models to investigate circadian regulation and facilitate exploration of clock function.


ABSTRACT: The circadian clock is an important adaptation to life on Earth. Here, we use machine learning to predict complex, temporal, and circadian gene expression patterns in Arabidopsis Most significantly, we classify circadian genes using DNA sequence features generated de novo from public, genomic resources, facilitating downstream application of our methods with no experimental work or prior knowledge needed. We use local model explanation that is transcript specific to rank DNA sequence features, providing a detailed profile of the potential circadian regulatory mechanisms for each transcript. Furthermore, we can discriminate the temporal phase of transcript expression using the local, explanation-derived, and ranked DNA sequence features, revealing hidden subclasses within the circadian class. Model interpretation/explanation provides the backbone of our methodological advances, giving insight into biological processes and experimental design. Next, we use model interpretation to optimize sampling strategies when we predict circadian transcripts using reduced numbers of transcriptomic timepoints. Finally, we predict the circadian time from a single, transcriptomic timepoint, deriving marker transcripts that are most impactful for accurate prediction; this could facilitate the identification of altered clock function from existing datasets.

SUBMITTER: Gardiner LJ 

PROVIDER: S-EPMC8364196 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Interpreting machine learning models to investigate circadian regulation and facilitate exploration of clock function.

Gardiner Laura-Jayne LJ   Rusholme-Pilcher Rachel R   Colmer Josh J   Rees Hannah H   Crescente Juan Manuel JM   Carrieri Anna Paola AP   Duncan Susan S   Pyzer-Knapp Edward O EO   Krishna Ritesh R   Hall Anthony A  

Proceedings of the National Academy of Sciences of the United States of America 20210801 32


The circadian clock is an important adaptation to life on Earth. Here, we use machine learning to predict complex, temporal, and circadian gene expression patterns in <i>Arabidopsis</i> Most significantly, we classify circadian genes using DNA sequence features generated de novo from public, genomic resources, facilitating downstream application of our methods with no experimental work or prior knowledge needed. We use local model explanation that is transcript specific to rank DNA sequence feat  ...[more]

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