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Sumin Jo

Publications and source records attributed to Sumin Jo.

5 recordsLinked to original sources

m6A-FORM: An m6A-focused Foundation Model for Decoding m6A Regulatory Function

N6-methyladenosine (m6A) regulates mRNA fate through site-specific methylation, reader recognition and downstream effects on RNA stability and decay. However, current computational approaches focus mainly on site prediction, leaving unresolved the broader challenge of inferring m6A regulatory context and function from epitranscriptomic profiles. Here we present m6A-FORM, an m6A-focused foundation model for for regulatory discovery. Pretrained on 24.9 million RNA sequence windows from 22.5 million MeRIP-seq regions across 143 human studies, m6A-FORM learns reusable representations of m6A-associated transcript contexts. We adapt this encoder to single-nucleotide m6A discovery, regulator-binding prediction, YTHDF2-associated decay prediction and tissue-scale epitranscriptomic mapping. m6A-FORM predicts binding of 19 m6A readers, writers and erasers and identifies sequence and RBP-context features associated with YTHDF2-mediated RNA degradation. Applied to 67 datasets from 24 human tissues, it identifies tissue-conserved m6A sites linked to stronger methylation, reader binding, RBP occupancy and decay propensity.

q-bio.GN

R2-KG: General-Purpose Dual-Agent Framework for Reliable Reasoning on Knowledge Graphs

Recent studies have combined Large Language Models (LLMs) with Knowledge Graphs (KGs) to enhance reasoning, improving inference accuracy without additional training while mitigating hallucination. However, existing frameworks still suffer two practical drawbacks: they must be re-tuned whenever the KG or reasoning task changes, and they depend on a single, high-capacity LLM for reliable (i.e., trustworthy) reasoning. To address this, we introduce R2-KG, a plug-and-play, dual-agent framework that separates reasoning into two roles: an Operator (a low-capacity LLM) that gathers evidence and a Supervisor (a high-capacity LLM) that makes final judgments. This design is cost-efficient for LLM inference while still maintaining strong reasoning accuracy. Additionally, R2-KG employs an Abstention mechanism, generating answers only when sufficient evidence is collected from KG, which significantly enhances reliability. Experiments across five diverse benchmarks show that R2-KG consistently outperforms baselines in both accuracy and reliability, regardless of the inherent capability of LLMs used as the Operator. Further experiments reveal that the single-agent version of R2-KG, equipped with a strict self-consistency strategy, achieves significantly higher-than-baseline reliability with reduced inference cost but increased abstention rate in complex KGs. Our findings establish R2-KG as a flexible and cost-effective solution for KG-based reasoning, reducing reliance on high-capacity LLMs while ensuring trustworthy inference. The code is available at https://github.com/ekrxjwh2009/R2-KG/.

cs.CL

Time is Not Enough: Time-Frequency based Explanation for Time-Series Black-Box Models

Despite the massive attention given to time-series explanations due to their extensive applications, a notable limitation in existing approaches is their primary reliance on the time-domain. This overlooks the inherent characteristic of time-series data containing both time and frequency features. In this work, we present Spectral eXplanation (SpectralX), an XAI framework that provides time-frequency explanations for time-series black-box classifiers. This easily adaptable framework enables users to "plug-in" various perturbation-based XAI methods for any pre-trained time-series classification models to assess their impact on the explanation quality without having to modify the framework architecture. Additionally, we introduce Feature Importance Approximations (FIA), a new perturbation-based XAI method. These methods consist of feature insertion, deletion, and combination techniques to enhance computational efficiency and class-specific explanations in time-series classification tasks. We conduct extensive experiments in the generated synthetic dataset and various UCR Time-Series datasets to first compare the explanation performance of FIA and other existing perturbation-based XAI methods in both time-domain and time-frequency domain, and then show the superiority of our FIA in the time-frequency domain with the SpectralX framework. Finally, we conduct a user study to confirm the practicality of our FIA in SpectralX framework for class-specific time-frequency based time-series explanations. The source code is available in https://github.com/gustmd0121/Time_is_not_Enough

cs.LG

Understanding YTHDF2-mediated mRNA Degradation By m6A-BERT-Deg

N6-methyladenosine (m6A) is the most abundant mRNA modification within mammalian cells, holding pivotal significance in the regulation of mRNA stability, translation, and splicing. Furthermore, it plays a critical role in the regulation of RNA degradation by primarily recruiting the YTHDF2 reader protein. However, the selective regulation of mRNA decay of the m6A-methylated mRNA through YTHDF2 binding is poorly understood. To improve our understanding, we developed m6A-BERT-Deg, a BERT model adapted for predicting YTHDF2-mediated degradation of m6A-methylated mRNAs. We meticulously assembled a high-quality training dataset by integrating multiple data sources for the HeLa cell line. To overcome the limitation of small training samples, we employed a pre-training-fine-tuning strategy by first performing a self-supervised pre-training of the model on 427,760 unlabeled m6A site sequences. The test results demonstrated the importance of this pre-training strategy in enabling m6A-BERT-Deg to outperform other benchmark models. We further conducted a comprehensive model interpretation and revealed a surprising finding that the presence of co-factors in proximity to m6A sites may disrupt YTHDF2-mediated mRNA degradation, subsequently enhancing mRNA stability. We also extended our analyses to the HEK293 cell line, shedding light on the context-dependent YTHDF2-mediated mRNA degradation.

q-bio.MN

Deep learning tackles single-cell analysis A survey of deep learning for scRNA-seq analysis

Since its selection as the method of the year in 2013, single-cell technologies have become mature enough to provide answers to complex research questions. With the growth of single-cell profiling technologies, there has also been a significant increase in data collected from single-cell profilings, resulting in computational challenges to process these massive and complicated datasets. To address these challenges, deep learning (DL) is positioning as a competitive alternative for single-cell analyses besides the traditional machine learning approaches. Here we present a processing pipeline of single-cell RNA-seq data, survey a total of 25 DL algorithms and their applicability for a specific step in the processing pipeline. Specifically, we establish a unified mathematical representation of all variational autoencoder, autoencoder, and generative adversarial network models, compare the training strategies and loss functions for these models, and relate the loss functions of these models to specific objectives of the data processing step. Such presentation will allow readers to choose suitable algorithms for their particular objective at each step in the pipeline. We envision that this survey will serve as an important information portal for learning the application of DL for scRNA-seq analysis and inspire innovative use of DL to address a broader range of new challenges in emerging multi-omics and spatial single-cell sequencing.

q-bio.GN