研究成果

Animal growth is driven by the collective actions of cells, which are reciprocally influenced in real-time by the animal's overall growth state. Whereas cell behavior and animal growth state are expected to be tightly coupled, it is not yet determined whether local cellular features at the micrometer scale might correlate with the body size of an animal at the macroscopic level. By inputting 722 skin cell images and corresponding size data for each zebrafish larva into machine learning models, we determined that the Vision Transformer (ViT) with a random cropping and voting strategy was able to achieve high predictive performance (F-score of 0.91). Remarkably, analyzing as few as 27 skin cells within a single image of 0.01 mm2 was sufficient to predict the individual's overall...

Trichomes in Prunus persica (L.) Batsch are crucial specialized structures that play a protective role against both biotic and abiotic stresses. The fruits with and without trichomes are respectively named as peach and nectarine. At the genetic level, the formation of trichome in peach is controlled by a single gene, PpMYB25, at the G locus. Peach (GG or Gg) is dominant to nectarine (gg), but such regulatory role was reported in a small-scale accession. In this study, we performed large-scale genotype and phenotype screening on 295 accessions. Almost all accessions supported the casual relationship between trichome formation and PpMYB25. However, a peach to nectarine mutant, named Maravilha Nectarine Mutant (MN), was discovered to possess a putative functional PpMYB25 gene sequence (Gg)...

Background: Pathogenic variants in OTOF are a major cause of auditory synaptopathy. However, challenges remain in interpreting OTOF variants, including difficulties in confirming haplotype phasing using traditional short-read sequencing (SRS) due to the large gene size, the potential incomplete penetrance of certain variants, and difficulties in assessing variants at non-canonical splice sites. This study aims to revisit the genetic landscape of OTOF variants in a Taiwanese non-syndromic auditory neuropathy spectrum disorder (ANSD) cohort using a combination of sequencing technologies, predictive tools, and experimental validations. Methods: We performed SRS to analyze OTOF variants in 65 unrelated Taiwanese patients diagnosed with non-syndromic ANSD, complemented by long-read sequencing...

Background: Atrial fibrillation (AF) is a major risk factor for transient ischemic attack (TIA)/ischemic stroke (IS). Objectives: Given the dynamic nature of IS risk, this study aimed to predict IS risk in AF patients using a high-dimensional time-series model. Methods: We conducted a cohort study at the National Taiwan University Hospital from 2014 to 2019, including 7,710 AF patients, with external validation in 6,822 patients from the National Taiwan University Hospital Yunlin Branch. The Forecasting Strokes via Interpretable Independent Networks (ForeSIIN) model, based on gated recurrent units, was proposed. Kaplan-Meier analysis with log-rank test evaluated risk group differences. Results: The annual TIA/IS incidence rate ranged from 181.96 (95% CI: 164.42-200.93) to 15.81 (95% CI:...

Breast cancer stands as one of the most prevalent malignancies affecting women. Alterations in molecular pathways in cancer cells represent key regulatory disruptions that drive malignancy, influencing cancer cell survival, proliferation, and potentially modulating therapeutic responsiveness. Therefore, decoding the intricate molecular mechanisms and identifying novel therapeutic targets through systematic computational approaches are essential steps toward advancing effective breast cancer treatments. In this study, we developed an integrative computational framework that combines single-cell RNA sequencing (scRNA-seq) and multi-omics analyses to delineate the functional characteristics of malignant cell subsets in breast cancer patients. Our analyses revealed a significant correlation...

Neuroblastoma is an aggressive childhood cancer that arises from the sympathetic nervous system. Despite advances in treatment, high-risk neuroblastoma remains difficult to manage due to its heterogeneous nature and frequent development of drug resistance. Drug repurposing guided by single-cell analysis presents a promising strategy for identifying new therapeutic options. Here, we aim to characterize high-risk neuroblastoma subpopulations and identify effective repurposed drugs for targeted treatment. We performed single-cell transcriptomic analysis of neuroblastoma samples, integrating bulk RNA-seq data deconvolution with clinical outcomes to define distinct malignant cell states. Using a systematic drug repurposing pipeline, we identified and validated potential therapeutic agents...

Betalains, a group of pigments widely distributed in various plants, are extensively applied in the food, beverage, and medicinal industries. The biosynthesis of betalains involves the enzymatic action of 4,5-DOPA-dioxygenase, which catalyzes the key ring-opening reaction of DOPA to produce betalamic acid, a crucial intermediate in the pathway. The crystal structure of a 4,5-DOPA-dioxygenase from Beta vulgaris (BvDOD) was determined in this study. The structural analysis revealed that BvDOD exhibited a structural fold similar to that of other members of the extradiol dioxygenase family. Moreover, the Fe-ligand residues His15, His53, and His229 indicated the enzyme's reliance on nonheme iron for catalyzing the ring-opening reaction. Molecular docking and mutational analysis identified...

Human hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer-related deaths worldwide. HCC is a malignant tumor that can lead to intrahepatic and extrahepatic metastases. Intercellular adhesion molecule 1 (ICAM-1) is involved in cancer metastasis. ICAM-1 enhances cell-cell interactions by promoting adhesion and facilitating cell movement within the extracellular matrix. Moreover, ICAM-1 is more abundant in cancerous hepatocytes than in non-cancerous ones. Chemokine (C-X-C motif) ligand 1 (CXCL1) is found in diverse cancers, including melanoma, breast, lung, pancreatic, colorectal, and prostate. Several studies show a correlation between CXCL1 overexpression and poor prognosis in cancer. CXCL1 has been identified as a candidate gene that could...

Background: Sepsis is characterized by organ dysfunction as a response to infection and is one of the leading causes of mortality and loss of health. The heterogeneous nature of sepsis, along with ethnic differences in susceptibility, challenges a thorough understanding of its etiology. This study aimed to propose prediction models by leveraging genetic-risk scores and clinical variables that can assist in risk stratification of patients. Methods: A total of 1,403 patients from Taiwan, diagnosed with sepsis, were utilized. Genome-wide survival analysis was conducted, with death within 28 days from sepsis onset, as the primary event to report significantly associated SNPs. A polygenic risk score (PRS-sepsis) was constructed via clumping and thresholding method which was added to clinical-...

Structural variants (SVs) have been associated with changes in gene expression, which may contribute to alterations in phenotypes and disease development. However, the precise identification and characterization of SVs remain challenging. While long-read sequencing offers superior accuracy for SV detection, short-read sequencing remains essential due to practical and cost considerations, as well as the need to analyze existing short-read datasets. Numerous algorithms for short-read SV detection exist, but none are universally optimal, each having limitations for specific SV sizes and types. In this study, we evaluated the efficacy of six advanced SV detection algorithms, including the commercial software DRAGEN, using the GIAB v0.6 Tier 1 benchmark and HGSVC2 cell lines. We employed both...