Biology subjects

Teo, G.

Publications and source records attributed to Teo, G..

5 recordsLinked to original sources

bioRxiv2025

MRMhub: one-stop solution for automated processing of large-scale targeted metabolomics data

Data processing and quality control are essential for complex targeted mass spectrometry (MS) assays in large-scale metabolomics studies. However, existing software solutions have significant gaps in robustness and scalability. We report MRMhub, a one-stop solution for streamlined processing of large-scale targeted MS data. MRMhub consists of a novel peak integration engine with unique algorithmic design to address the scalability challenge and a comprehensive collection of post-acquisition data processing and analytical quality control tools. The ensemble facilitates rapid and consistent processing of complex chromatograms, quantification, drift and batch correction, quality assessment and control, feature filtering, and data/workflow sharing and reporting. MRMhub can process data from highly complex assays in population-scale studies within minutes, with full digital footprints warranting reproducibility and traceability. We demonstrate its performance using two large-scale lipidomics data sets. We distribute the source code and data sets freely for community development.

bioinformatics↗

bioRxiv2025

Omics-based insights into human liver reveal GTPase-driven mechanisms of MASLD progression in obesity

Metabolic dysfunction-associated steatotic liver disease (MASLD) is often asymptomatic early on but can progress to irreversible conditions like cirrhosis. Due to limited access to human liver biopsies, systematic and integrative molecular resources remain scarce. In this study, we performed transcriptomic analyses on liver and metabolomic analyses on liver and plasma samples from morbidly obese individuals without liver pathology or at early-stage MASLD. While, the plasma metabolomic profile did not fully mirror liver histological features, dual-omics integration of liver samples revealed significantly remodeled lipid and amino acid metabolism pathways. Integrative network analysis uncoupled metabolic remodeling and gene expression as independent features of hepatic steatosis and fibrosis progression, respectively. Notably, GTPases and their regulators emerged as a novel class of genes linked to early liver fibrosis. This study offers a detailed molecular landscape of early MASLD in obesity and highlights potential targets of obesity-linked liver fibrosis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/632747v3_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1188eborg.highwire.dtl.DTLVardef@1340070org.highwire.dtl.DTLVardef@108d560org.highwire.dtl.DTLVardef@f0adda_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

Context specific ubiquitin modification of ribosomes regulate translation under oxidative stress

Cellular exposure to stress is known to activate several translational control pathways through ribosome ubiquitination. However, how unique patterns of ribosome ubiquitination act at the site-specific level to drive distinct modes of translation regulation remains unclear. To further understand the complexity of these ubiquitin signals, we developed a new targeted proteomics approach to quantify site-specific ubiquitin modification across the ribosome. This method increased the sensitivity and throughput of current approaches and allowed us to systematically measure the ubiquitin status of 78 ribosome peptides and ubiquitin linkages in response to stress. Using this method, we were able to detect the ubiquitination of several ribosome sites even in steady-state conditions, and to show that their modification increases non-stoichiometrically in a dynamic range of >4 orders of magnitude in response to hydrogen peroxide. Besides demonstrating new patterns of global ribosome ubiquitination, our study also revealed an unexpected increase of ubiquitination of ribosomal protein uS10/Rps20 and uS3/Rps3 independent of the canonical E3 ubiquitin ligase Hel2. Furthermore, we show that unique and mixed patterns of ribosome ubiquitination occur in a stress specific manner, depending on the nature of stressor and the enzymes involved. Finally, we showed that while deletion of HEL2 further induces the integrated stress response in response to the nucleotide alkylating agent 4-NQO, deletion of the E2 conjugase RAD6 leads to sustained translation only in response to H2O2. Our findings contribute to deciphering the complexity of the stress response at the translational level, revealing the induction of dynamic and selective ubiquitin codes, which shed light on the integration of important quality control pathways during cellular response to stress.

molecular biology↗

bioRxiv2019

Multi-omics profiling of CHO parental hosts reveals cell line-specific variations in bioprocessing traits

Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human-like post-translational modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines have been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO-K1, CHO-DXB11 and CHO-DG44) in suspension cultures and further report their growth-related characteristics, and N- and O-glycosylation patterns of host cell proteins (HCPs). The comparative multi-omics analysis indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N- and O-glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced.

systems biology↗

bioRxiv2018

Quantifying multi-layered expression regulation in response to stress of the endoplasmic reticulum

The mammalian response to endoplasmic reticulum (ER) stress dynamically affects all layers of gene expression regulation. We quantified transcript and protein abundance along with footprints of ribosomes and non-ribosomal proteins for thousands of genes in cervical cancer cells responding to treatment with tunicamycin or hydrogen peroxide over an eight hour time course. We identify shared and stress-specific significant regulatory events at the transcriptional and post-transcriptional level and at different phases of the experiment. ER stress regulators increase transcription and translation at different times supporting an adaptive response. ER stress also induces translation of genes from serine biosynthesis and one-carbon metabolism indicating a shift in energy production. Discordant regulation of DNA repair genes suggests transcriptional priming in which delayed translation fine-tunes the early change in the transcriptome. Finally, case studies on stress-dependent alternative splicing and protein-mRNA binding demonstrate the ability of this resource to generate hypotheses for new regulatory mechanisms.

systems biology↗