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  4. Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations
 
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conference paper

Towards improving full-length ribosome density prediction by bridging sequence and graph-based representations

Nallapareddy, Mohan Vamsi  
•
Craighero, Francesco  
•
Naef, Felix  
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2024
Proceedings of the 19th Machine Learning in Computational Biology meeting
19th Machine Learning in Computational Biology meeting

Translation elongation plays an important role in regulating protein concentrations in the cell, and dysregulation of this process has been linked to several human diseases. In this study, we use data from ribo-seq experiments to model ribosome densities, and in turn, predict the speed of translation. The proposed method, RiboGL, combines graph and recurrent neural networks to account for both graph and sequence-based features. The model takes a graph representing the secondary structure of the mRNA sequence as input, which incorporates both sequence and structural codon neighbors. In our experiments, RiboGL greatly outperforms the state-of-the-art RiboMIMO model for ribosome density prediction. We also conduct ablation studies to justify the design choices made in building the pipeline. Additionally, we use gradient-based interpretability to understand how the codon context and the structural neighbors affect the ribosome density at the A-site. By individually analyzing the genes in the dataset, we elucidate how structural neighbors could also potentially play a role in defining the ribosome density. Importantly, since these neighbors can be far away in the sequence, a recurrent model alone could not easily extract this information. This study lays the foundation for understanding how the mRNA secondary structure can be exploited for ribosome density prediction, and how in the future other graph modalities such as features from the nascent polypeptide can be used to further our understanding of translation in general.

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Type
conference paper
Author(s)
Nallapareddy, Mohan Vamsi  
•
Craighero, Francesco  
•
Naef, Felix  
•
Gobet, Cédric  
•
Vandergheynst, Pierre  
Date Issued

2024

Publisher

PMLR

Published in
Proceedings of the 19th Machine Learning in Computational Biology meeting
Book part number

261:38-52

Series title/Series vol.

Proceedings of Machine Learning Research; 261

ISSN (of the series)

2640-3498

Subjects

Graph Neural Networks

•

Ribosome Density Prediction

•

Graph Interpretability

URL

Link to conference paper

https://proceedings.mlr.press/v261/nallapareddy24a.html
Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LTS2  
UPNAE  
Event nameEvent acronymEvent placeEvent date
19th Machine Learning in Computational Biology meeting

MLCB

Seattle, WA, USA

2024-09-05 - 2024-09-06

FunderFunding(s)Grant NumberGrant URL

Swiss National Science Foundation

Integrated multi-scale analysis of translation: single-molecules, omics and computation

CRSII5_205884/1

https://data.snf.ch/grants/grant/205884
RelationURL/DOI

IsSupplementedBy

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73553
Available on Infoscience
March 5, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/207062.2
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