Optical pooled screening (OPS) has emerged as a powerful technique for functional genomics, enabling researchers to link genetic perturbations with complex cellular morphological phenotypes at unprecedented scale. However, OPS data analysis presents challenges due to massive datasets, complex multi-modal integration requirements, and the absence of standardized frameworks. Here, we present Brieflow, a computational pipeline for end-to-end analysis of fixed-cell optical pooled screening data.
View Article and Find Full Text PDFMitochondrial endosymbiosis was a pivotal event in eukaryotic evolution, requiring core proteins to adapt to function both within the mitochondria and in the host cell. Here, we systematically profile the localization of protein isoforms generated by alternate start codon selection during translation. We identify hundreds of pairs of differentially-localized protein isoforms, many of which affect mitochondrial targeting and are essential for mitochondrial function.
View Article and Find Full Text PDFDirected protein evolution is central to biomedical applications but faces challenges such as experimental complexity, inefficient multiproperty optimization, and local maxima traps. Although in silico methods that use protein language models (PLMs) can provide modeled fitness landscape guidance, they struggle to generalize across diverse protein families and map to protein activity. We present EVOLVEpro, a few-shot active learning framework that combines PLMs and regression models to rapidly improve protein activity.
View Article and Find Full Text PDFPurpose: The incidence of GI cancers is increasing in sub-Saharan African countries. We described the oncological care pathway and assessed presentation, diagnosis, and treatment intervals and delays among patients with GI cancer who presented to the Obafemi Awolowo University Teaching Hospitals Complex in Ile-Ife, Nigeria.
Methods: We analyzed data from 545 patients with GI cancer in the African Research Group for Oncology (ARGO) database.
Unlabelled: Although localized prostate cancer is relatively indolent, advanced prostate cancer manifests with aggressive and often lethal variants, including neuroendocrine prostate cancer (NEPC). To identify drivers of aggressive prostate cancer, we leveraged transposon mutagenesis in a mouse model based on prostate-specific loss-of-function of and . Compared with control mice, mice developed more aggressive prostate tumors, with increased incidence of metastasis.
View Article and Find Full Text PDFEcancermedicalscience
October 2023
Background: Axillary lymph node staging is essential for making therapeutic decisions and for prognostication. A minimum of ten lymph nodes is recommended for accurate staging. This study describes the process and outcomes of an audit cycle that resulted in a novel intervention instituted to improve concordance with guidelines.
View Article and Find Full Text PDFBackground: The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1, a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress.
View Article and Find Full Text PDFEcancermedicalscience
December 2022
Background: Breast cancer in the elderly population has not been evaluated in the Nigerian context. With the rising incidence of breast cancer and the changing demographics, it is likely that an increasing number of elderly patients will be managed in the coming years in Nigeria. This review describes the clinicopathological profile of elderly patients with breast cancer in a Nigerian database.
View Article and Find Full Text PDFLarge-scale ecological sampling can be difficult and costly, especially for organisms that are too small to be easily identified in a natural environment by eye. Typically, these microscopic floral and fauna are sampled by collecting substrates from nature and then separating organisms from substrates in the laboratory. In many cases, diverse organisms can be identified to the species-level using molecular barcodes.
View Article and Find Full Text PDFTo study the progression of bladder cancer from non-muscle-invasive to muscle-invasive disease, we have developed a novel toolkit that uses complementary approaches to achieve gene recombination in specific cell populations in the bladder urothelium , thereby allowing us to generate a new series of genetically engineered mouse models (GEMM) of bladder cancer. One method is based on the delivery of adenoviruses that express Cre recombinase in selected cell types in the urothelium, and a second uses transgenic drivers in which activation of inducible Cre alleles can be limited to the bladder urothelium by intravesicular delivery of tamoxifen. Using both approaches, targeted deletion of the and tumor suppressor genes specifically in basal urothelial cells gave rise to muscle-invasive bladder tumors.
View Article and Find Full Text PDFMitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress.
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