# Deep Learning for Elucidating Modifications to RNA—Status and Challenges Ahead

**Authors:** Sarah Rennie

PMC · DOI: 10.3390/genes15050629 · Genes · 2024-05-15

## TL;DR

This paper reviews how deep learning is used to study RNA modifications and RNA-binding proteins, highlighting current methods and future challenges.

## Contribution

The paper provides a comprehensive overview of deep learning applications in RNA modification studies and outlines key areas for future research.

## Key findings

- Deep learning models can predict RNA modifications based on sequence and secondary structure features.
- Model training strategies, including selection of negative regions and data splitting, are critical for accurate predictions.
- The paper identifies four key areas for advancing the field of RNA modification analysis using deep learning.

## Abstract

RNA-binding proteins and chemical modifications to RNA play vital roles in the co- and post-transcriptional regulation of genes. In order to fully decipher their biological roles, it is an essential task to catalogue their precise target locations along with their preferred contexts and sequence-based determinants. Recently, deep learning approaches have significantly advanced in this field. These methods can predict the presence or absence of modification at specific genomic regions based on diverse features, particularly sequence and secondary structure, allowing us to decipher the highly non-linear sequence patterns and structures that underlie site preferences. This article provides an overview of how deep learning is being applied to this area, with a particular focus on the problem of mRNA-RBP binding, while also considering other types of chemical modification to RNA. It discusses how different types of model can handle sequence-based and/or secondary-structure-based inputs, the process of model training, including choice of negative regions and separating sets for testing and training, and offers recommendations for developing biologically relevant models. Finally, it highlights four key areas that are crucial for advancing the field.

## Full-text entities

- **Genes:** HNRNPD (heterogeneous nuclear ribonucleoprotein D) [NCBI Gene 3184] {aka AUF1, AUF1A, HNRPD, P37, hnRNPD0}, TARDBP (TAR DNA binding protein) [NCBI Gene 23435] {aka ALS10, TDP-43}, SRSF1 (serine and arginine rich splicing factor 1) [NCBI Gene 6426] {aka ASF, NEDFBA, SF2, SF2p33, SFRS1, SRp30a}, FUS (FUS RNA binding protein) [NCBI Gene 2521] {aka ALS6, ETM4, FUS1, HNRNPP2, POMP75, TLS}, RNPC3 (RNA binding region (RNP1, RRM) containing 3) [NCBI Gene 55599] {aka CPHD7, IGHD5, RBM40, RNP, SNRNP65}, ADAR (adenosine deaminase RNA specific) [NCBI Gene 103] {aka ADAR1, AGS6, DRADA, DSH, DSRAD, G1P1}, YTHDC1 (YTH N6-methyladenosine RNA binding protein C1) [NCBI Gene 91746] {aka YT521, YT521-B}, ELAVL1 (ELAV like RNA binding protein 1) [NCBI Gene 1994] {aka ELAV1, HUR, Hua, MelG}, RBMS3 (RNA binding motif single stranded interacting protein 3) [NCBI Gene 27303], DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161] {aka CASC7, EIF2C2, LESKRES, LINC00980, PPD, Q10}, METAP2 (methionyl aminopeptidase 2) [NCBI Gene 10988] {aka MAP2, MNPEP, p67eIF2}, PABPC4 (poly(A) binding protein cytoplasmic 4) [NCBI Gene 8761] {aka APP-1, APP1, PABP4, iPABP}, ALKBH5 (alkB homolog 5, RNA demethylase) [NCBI Gene 54890] {aka ABH5, OFOXD, OFOXD1}, DDX55 (DEAD-box helicase 55) [NCBI Gene 57696]
- **Diseases:** -so (MESH:C565984), injury to people or property (MESH:C000719191)
- **Chemicals:** m6A (MESH:C005955), N6-methyladenosine (MESH:C010223), m5-cytosine (-), pseudouridine (MESH:D011560)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HEK293T. — Homo sapiens (Human), Transformed cell line (CVCL_0063), K562 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Full text

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## Figures

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## References

100 references — full list in the complete paper: https://tomesphere.com/paper/PMC11121098/full.md

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Source: https://tomesphere.com/paper/PMC11121098