Research on long non-coding RNAs (lncRNAs) has garnered significant attention due to their critical roles in gene regulation and disease mechanisms. However, the complexity and diversity of lncRNA sequences, along with the limited knowledge of their functional mechanisms and the regulation of their expressions, pose significant challenges to lncRNA studies. Given the tremendous success of large language models (LLMs) in capturing complex dependencies in sequential data, this study aims to systematically explore the potential and limitations of LLMs in the sequence analysis related to the transcriptional regulation of lncRNA genes. Our extensive experiments demonstrated promising performance of fine-tuned genome foundation models on progressively complex tasks. Furthermore, we conducted an insightful analysis of the critical impact of task complexity, model selection, data quality, and biological interpretability for the studies of the regulation of lncRNA gene expression.

Gene essentiality refers to the degree to which a gene is necessary for the survival and reproductive efficacy of a living organism. Although the essentiality of non-coding genes has been documented, there are still aspects of non-coding genes' essentiality that are unknown to us. For example, We do not know the contribution of sequence features and network spatial features to essentiality. As a consequence, in this work, we propose DeepHEN that could answer the above question. By buidling a new lncRNA-proteion-protein network and utilizing both representation learning and graph neural network, we successfully build our DeepHEN models that could predict the essentiality of lncRNA genes. Compared to other methods for predicting the essentiality of lncRNA genes, our DeepHEN model not only tells whether sequence features or network spatial features have a greater influence on essentiality but also addresses the overfitting issue of those methods caused by the low number of essential lncRNA genes, as evidenced by the results of enrichment analysis. Keywords: sample, graph neural network, representation learing, lncRNA-protein-protein network, essential non-coding genes INTORDUCTION Gene essentiality refers to the degree to which a gene is necessary for the survival and reproductive success of a living system. Genes that are indispensable in fulfilling these functions are classified as essential genes[1]. The concept of gene essentiality is dynamic and influenced by the specific context in which it is assessed.