Short tandem repeats (STRs) have been reported to influence gene expression across various human tissues. While STR variations are enriched in colorectal, stomach, and endometrial cancers, particularly in microsatellite instable tumors, their functional effects and regulatory mechanisms on gene expression remain poorly understood across these cancer types. Here, we leverage whole-exome sequencing and gene expression data to identify STRs for which repeat lengths are associated with the expression of nearby genes (eSTRs) in colorectal, stomach, and endometrial tumors. While most eSTRs are cancer-specific, shared eSTRs across multiple cancers exhibit consistent effects on gene expression. Notably, coding-region eSTRs identified in all three cancer types show positive correlations with nearby gene expression. We further validate the functional effects of eSTRs by demonstrating associations between somatic eSTR mutations and gene expression changes during the transition from normal to tumor tissues, suggesting their potential roles in tumorigenesis. Combined with DNA methylation data, we perform the first quantitative analysis of the interplay between STR variations and DNA methylation in tumors. We identify eSTRs where repeat lengths are associated with methylation levels of nearby CpG sites (meSTRs) and show that >70% of eSTRs are significantly linked to local DNA methylation. Importantly, the effects of meSTRs on DNA methylation remain consistent across cancer types. Overall, our findings enhance the understanding of how functional STR variations influence gene expression and DNA methylation. Our study highlights shared regulatory mechanisms of STRs across multiple cancers, offering a foundation for future research into their broader implications in tumor biology.

Maritime operations are increasingly reliant on sensor data to drive efficiency and enhance decision-making. However, despite rapid advances in large language models, including expanded context windows and stronger generative capabilities, critical industrial settings still require secure, role-constrained access to enterprise data and explicit limitation of model context. Retrieval-Augmented Generation (RAG) remains essential to enforce data minimization, preserve privacy, support verifiability, and meet regulatory obligations by retrieving only permissioned, provenance-tracked slices of information at query time. However, current RAG solutions lack robust validation protocols for numerical accuracy for high-stakes industrial applications. This paper introduces Lighthouse Bot, a novel Agentic RAG system specifically designed to provide natural-language access to complex maritime sensor data, including time-series and relational sensor data. The system addresses a critical need for verifiable autonomous data analysis within the Artificial Intelligence of Things (AIoT) domain, which we explore through a case study on optimizing ferry operations. We present a detailed architecture that integrates a Large Language Model with a specialized database and coding agents to transform natural language into executable tasks, enabling core AIoT capabilities such as generating Python code for time-series analysis, executing complex SQL queries on relational sensor databases, and automating workflows, while keeping sensitive data outside the prompt and ensuring auditable, policy-aligned tool use. To evaluate performance, we designed a test suite of 24 questions with ground-truth answers, categorized by query complexity (simple, moderate, complex) and data interaction type (retrieval, aggregation, analysis). Our results show robust, controlled data access with high factual fidelity: the proprietary Claude 3.7 achieved close to 90% overall factual correctness, while the open-source Qwen 72B achieved 66% overall and 99% on simple retrieval and aggregation queries. These findings underscore the need for a secure limited-context RAG in maritime AIoT and the potential for cost-effective automation of routine exploratory analyses.

Background Short tandem repeats (STRs) have been reported to influence gene expression across various human tissues. While STR variations are enriched in colorectal (CRC), stomach (STAD) and endometrial (UCEC) cancers, particularly in microsatellite instable (MSI) tumors, their functional effects and regulatory mechanisms on gene expression remain poorly understood across these cancer types. Results Here, we leverage whole-exome sequencing and gene expression data to identify STRs for which repeat lengths are associated with the expression of nearby genes (eSTRs) in CRC, STAD and UCEC tumors. Our analyses reveal that tumor STR profiles effectively capture both MSI phenotype and population structure. While most eSTRs are cancer-specific, shared eSTRs across multiple cancers exhibit consistent effects on gene expression. Notably, coding-region eSTRs identified in all three cancer types show positive correlations with nearby gene expression. We further validate the functional effects of eSTRs by demonstrating associations between somatic eSTR mutations and gene expression changes during the transition from normal to tumor tissues, suggesting their potential roles in tumorigenesis. Combined with DNA methylation data, we perform the first quantitative analysis of the interplay between STR variations and 1 DNA methylation in tumors. We identify eSTRs where repeat lengths are associated with methylation levels of nearby CpG sites (meSTRs) and show that over 70% of eSTRs are significantly linked to local DNA methylation. Importantly, the effects of meSTRs on DNA methylation remain consistent across cancer types. Conclusions Overall, our findings enhance the understanding of how functional STR variations influence gene expression and DNA methylation. Our study highlights shared regulatory mechanisms of STRs across multiple cancers, offering a foundation for future research into their broader implications in tumor biology.

Background: Short tandem repeats (STRs) have been reported to influence gene expression across various human tissues. While STR variations are enriched in colorectal (CRC), stomach (STAD) and endometrial (UCEC) cancers, particularly in microsatellite instable (MSI) tumors, their functional effects and regulatory mechanisms on gene expression remain poorly understood across these cancer types. Results: Here, we leverage whole-exome sequencing and gene expression data to identify STRs for which repeat lengths are associated with the expression of nearby genes (eSTRs) in CRC, STAD and UCEC tumors. Our analyses reveal that tumor STR profiles effectively capture both MSI phenotype and population structure. While most eSTRs are cancer-specific, shared eSTRs across multiple cancers exhibit consistent effects on gene expression. Notably, coding-region eSTRs identified in all three cancer types show positive correlations with nearby gene expression. We further validate the functional effects of eSTRs by demonstrating associations between somatic eSTR mutations and gene expression changes during the transition from normal to tumor tissues, suggesting their potential roles in tumorigenesis. Combined with DNA methylation data, we perform the first quantitative analysis of the interplay between STR variations and DNA methylation in tumors. We identify eSTRs where repeat lengths are associated with methylation levels of nearby CpG sites (meSTRs) and show that over 70% of eSTRs are significantly linked to local DNA methylation. Importantly, the effects of meSTRs on DNA methylation remain consistent across cancer types. Conclusions: Overall, our findings enhance the understanding of how functional STR variations influence gene expression and DNA methylation. Our study highlights shared regulatory mechanisms of STRs across multiple cancers, offering a foundation for future research into their broader implications in tumor biology.

Short tandem repeat (STR) mutations are prevalent in colorectal cancer (CRC), especially in tumours with the microsatellite instability (MSI) phenotype. While STR length variations are known to regulate gene expression under physiological conditions, the functional impact of STR mutations in CRC remains unclear. Here, we integrate STR mutation data with clinical information and gene expression levels to study the gene regulatory effects of STR mutations in CRC. We confirm that STR mutability in CRC highly depends on the MSI status, repeat unit size, and repeat length. Furthermore, we present a set of 1244 putative expression STRs (eSTRs) for which the STR length is associated with gene expression levels in CRC tumours. The length of 73 eSTRs is associated with expression levels of cancer-related genes, nine of which are CRC-specific genes. We show that linear models describing eSTR-gene expression relationships allow for predictions of gene expression changes in response to eSTR mutations. Moreover, we found an increased mutability of eSTRs in MSI tumours. Our evidence of gene regulatory roles for eSTRs in CRC highlights a mostly overlooked way through which tumours may modulate their phenotypes. The increased mutability of eSTRs in MSI tumours may be an early indication that eSTR mutations can confer a selective advantage to tumours. Future extensions of our findings into larger cohorts could uncover new STR-based targets in the treatment of cancer.