STW-MD: A Novel Spatio-Temporal Weighting and Multi-Step Decision Tree Method for Considering Spatial Heterogeneity in Brain Gene Expression Data

Motivation: Gene expression during brain development or abnormal development is a biological process that is highly dynamic in spatio and temporal. Due to the lack of comprehensive integration of spatial and temporal dimensions of brain gene expression data, previous studies have mainly focused on individual brain regions or a certain developmental stage. Our motivation is to address this gap by incorporating spatio-temporal information to gain a more complete understanding of the mechanisms underlying brain development or disorders associated with abnormal brain development, such as Alzheimer's disease (AD), and to identify potential determinants of response. Results: In this study, we propose a novel two-step framework based on spatial-temporal information weighting and multi-step decision trees. This framework can effectively exploit the spatial similarity and temporal dependence between different stages and different brain regions, and facilitate differential gene analysis in brain regions with high heterogeneity. We focus on two datasets: the AD dataset, which includes gene expression data from early, middle, and late stages, and the brain development dataset, spanning fetal development to adulthood. Our findings highlight the advantages of the proposed framework in discovering gene classes and elucidating their impact on brain development and AD progression across diverse brain regions and stages. These findings align with existing studies and provide insights into the processes of normal and abnormal brain development. Availability: The code of STW-MD is available at https://github.com/tsnm1/STW-MD.Comment: 11 pages, 6 figure

Priority index for critical Covid-19 identifies clinically actionable targets and drugs

Abstract While genome-wide studies have identified genomic loci in hosts associated with life-threatening Covid-19 (critical Covid-19), the challenge of resolving these loci hinders further identification of clinically actionable targets and drugs. Building upon our previous success, we here present a priority index solution designed to address this challenge, generating the target and drug resource that consists of two indexes: the target index and the drug index. The primary purpose of the target index is to identify clinically actionable targets by prioritising genes associated with Covid-19. We illustrate the validity of the target index by demonstrating its ability to identify pre-existing Covid-19 phase-III drug targets, with the majority of these targets being found at the leading prioritisation (leading targets). These leading targets have their evolutionary origins in Amniota (‘four-leg vertebrates’) and are predominantly involved in cytokine-cytokine receptor interactions and JAK-STAT signaling. The drug index highlights opportunities for repurposing clinically approved JAK-STAT inhibitors, either individually or in combination. This proposed strategic focus on the JAK-STAT pathway is supported by the active pursuit of therapeutic agents targeting this pathway in ongoing phase-II/III clinical trials for Covid-19