Publications by authors named "Venkata S Jonnakuti"
Article Synopsis
- Alternative polyadenylation (APA) is a crucial process that regulates gene expression, but its role in human diseases isn't well understood due to limitations in current research methods that use bulk RNA sequencing (RNA-seq).
- Existing RNA-seq methods struggle with predefined annotations and overlapping cleavage and polyadenylation sites (C/PASs), which means they miss important tissue- and disease-specific changes in APA.
- The new algorithm, PolyAMiner-Bulk, uses deep learning to effectively analyze and visualize APA dynamics, outperforming existing methods by accurately identifying more APA changes across various datasets.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3' endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that is highly expressed in PDAC and is associated with poor prognosis.
View Article and Find Full Text PDFPurpose: Gliomas and their surrounding microenvironment constantly interact to promote tumorigenicity, yet the underlying posttranscriptional regulatory mechanisms that govern this interplay are poorly understood.
Methods: Utilizing our established PAC-seq approach and PolyAMiner bioinformatic analysis pipeline, we deciphered the NUDT21-mediated differential APA dynamics in glioma cells.
Results: We identified LAMC1 as a critical NUDT21 alternative polyadenylation (APA) target, common in several core glioma-driving signaling pathways.
Article Synopsis
- Alternative polyadenylation (APA) produces different transcripts from a single gene by cleaving pre-mRNA at various poly(A) sites, primarily studied in the 3' untranslated region (3'UTR).
- The study highlights that insufficient CPSF6 leads to changes in protein levels and development issues by affecting APA across the transcript, not just in the 3'UTR.
- It was found that in humans and zebrafish, CPSF6 insufficiency alters poly(A) site usage, impacting neuronal genes by reducing their expression while enhancing expression of heart and skeletal function genes.
More than half of human genes exercise alternative polyadenylation (APA) and generate mRNA transcripts with varying 3' untranslated regions (UTR). However, current computational approaches for identifying cleavage and polyadenylation sites (C/PASs) and quantifying 3'UTR length changes from bulk RNA-seq data fail to unravel tissue- and disease-specific APA dynamics. Here, we developed a next-generation bioinformatics algorithm and application, PolyAMiner-Bulk, that utilizes an attention-based machine learning architecture and an improved vector projection-based engine to infer differential APA dynamics accurately.
View Article and Find Full Text PDFObjectives: The aim of this study was to quantify subchondral bone remodeling in the elbows, hands, knees, and feet using volumetric and metabolic parameters derived from F-sodium fluoride positron emission tomography (NaF-PET) and to assess the convergent validity of these parameters as an index of joint degeneration and preclinical osteoarthritis.
Methods: A retrospective analysis was conducted in 34 subjects (32 males, 2 females) with metastatic bone disease who underwent full-body NaF-PET/CT scans. An adaptive contrast-oriented thresholding algorithm was applied to segment NaF-avid regions in the bilateral elbows, hands, knees, and feet of each subject, and metabolically active volume (MAV), maximum standardized uptake value (SUVmax), mean metabolic volumetric product (MVPmean), and partial volume-corrected MVPmean (cMVPmean) of the segmented regions were calculated.
Aim: 2-deoxy-2-[ F]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) can portray increased glycolysis due to inflammation in rheumatoid arthritis (RA). The aim of this study was to evaluate and compare the reliability and construct validity of two methods of quantifying RA disease activity using FDG-PET/CT.
Method: Nineteen RA patients and 19 healthy controls matched to sex and age underwent prospective FDG-PET/CT imaging.
2-Deoxy-2-[F]fluoroglucose (FDG) uptake in muscle is influenced by many normal physiologic processes and can also indicate pathology. Variability in physiologic uptake can be reduced with proper patient preparation, allowing for a better determination of abnormal activity. Although malignant diseases, such as rhabdomyosarcoma and skeletal muscle metastasis, are clear applications of FDG-PET/CT, there may be additional applications in infection and benign inflammatory disorders that warrant further research.
View Article and Find Full Text PDFPurpose: Fluorine-18-sodium fluoride-PET ([F]NaF-PET) facilitates direct assessment of subchondral bone formation to evaluate degeneration in articulating joints. No standards exist for the quantification of joint activity using [F]NaF-PET, and many techniques rely on focal uptake to characterize an entire region of interest. This study proposes a novel method of quantitative global knee analysis to assess regions of expected bone remodeling in the evaluation of knee degeneration.
View Article and Find Full Text PDF