相关论文: Structural Investigations into Shwachman Bodian Di…
Structure-based drug design (SBDD) is a critical task in drug discovery, requiring the generation of molecular information across two distinct modalities: discrete molecular graphs and continuous 3D coordinates. However, existing SBDD…
Computational methods are needed to differentiate the small fraction of missense mutations that contribute to disease by disrupting protein function from neutral variants. We describe several complementary methods using large-scale homology…
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher…
Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…
Cardiovascular diseases (CVD) represent a major health issue in patients with schizophrneia (SCZ) and bipolar disorder (BD), but the exact nature of cardiometabolic (CM) abnormalities involved and the underlying mechanisms remain unclear.…
Here we use Drosophila melanogaster to create a genetic model of human permanent neonatal diabetes mellitus and present experimental results describing dimensions of this complexity. The approach involves the transgenic expression of a…
Identifying disease-indicative genes is critical for deciphering disease mechanisms and has attracted significant interest in biomedical research. Spatial transcriptomics offers unprecedented insights for the detection of disease-specific…
Background: Type 2 diabetes mellitus (T2DM) is increasingly recognised as a systemic disease characterised by coordinated dysfunction across metabolic, renal, lipid, and inflammatory pathways. Existing clinical assessments often fail to…
The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression…
Multiple Sclerosis (MS) is a chronic disease characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, and cognitive). Predicting disease progression with a probabilistic and time-dependent…
Structure-Based Drug Design (SBDD) is a powerful strategy in computational drug discovery, utilizing three-dimensional protein structures to guide the design of molecules with improved binding affinity. However, capturing complex…
Background: Structural Variations, SVs, in a genome can be linked to a disease or characteristic phenotype. The variations come in many types and it is a challenge, not only determining the variations accurately, but also conducting the…
It is widely held that a substantial genetic component underlies Bipolar Disorder (BD) and other neuropsychiatric disease traits. Recent efforts have been aimed at understanding the genetic basis of disease susceptibility, with genome-wide…
Schizophrenia (SZ) is a severe brain disorder marked by diverse cognitive impairments, abnormalities in brain structure, function, and genetic factors. Its complex symptoms and overlap with other psychiatric conditions challenge traditional…
Understanding alterations in structural disorders in tissue or cells or building blocks, such as DNA or chromatin in the human brain, at the nano to submicron level provides us with efficient biomarkers for Alzheimers detection. Here, we…
Fibrous dysplasia (FD) is a mosaic non-inheritable genetic disorder of the skeleton in which normal bone is replaced by structurally unsound fibro-osseous tissue. There is no curative treatment for FD, partly because its pathophysiology is…
Gene expression represents a fundamental interface between genes and environment in the development and ongoing plasticity of the human organism. Individual differences in gene expression are likely to underpin much of human diversity,…
After the completion of human genome sequence was anounced, it is evident that interpretation of DNA sequences is an immediate task to work on. For understanding their signals, improvement of present sequence analysis tools and developing…
Despite significant progress in dissecting the genetic architecture of complex diseases by genome-wide association studies (GWAS), the signals identified by association analysis may not have specific pathological relevance to diseases so…
We develop a Bayesian bivariate spatial model for multivariate regression analysis applicable to studies examining the influence of genetic variation on brain structure. Our model is motivated by an imaging genetics study of the Alzheimer's…