Machine learning a model for RNA structure prediction
2020-11-16
Nicola Calonaci, Alisha Jones, Francesca Cuturello, Michael Sattler and Giovanni Buss
RNA function crucially depends on its structure. Thermodynamic models currently used for secondary structure prediction rely on computing the partition function of folding ensembles, and can thus estimate minimum free-energy structures and ensemble populations. These models sometimes fail in identifying native structures unless complemented by auxiliary experimental data. Here, we build a set of models that combine thermodynamic parameters, chemical probing data (DMS and SHAPE) and co-evolutionary data (direct coupling analysis) through a network that outputs perturbations to the ensemble free energy. Perturbations are trained to increase the ensemble populations of a representative set of known native RNA structures. In the chemical probing nodes of the network, a convolutional window combines neighboring reactivities, enlightening their structural information content and the contribution of local conformational ensembles. Regularization is used to limit overfitting and improve transferability. The most transferable model is selected through a cross-validation strategy that estimates the performance of models on systems on which they are not trained. With the selected model we obtain increased ensemble populations for native structures and more accurate predictions in an independent validation set. The flexibility of the approach allows the model to be easily retrained and adapted to incorporate arbitrary experimental information.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
Office:
Würmtalstrasse 201
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77750
Fax: +49 (0)89 2180-77756
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Management: Dr. Nada Raddaoui
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 03.004
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77755
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 00.007
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77751
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website support: Martina Schuster
Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
Butenandtstr. 5 - 13
House D, Room 3.075
81377 Munich, Germany
Phone: +49 89 2180 77486
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Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77716
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Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77765
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