Biology subjects

Noureen, A.

Publications and source records attributed to Noureen, A..

3 recordsLinked to original sources

bioRxiv2023

Comparative Analysis of Whole Transcriptome Single-Cell Sequencing Technologies in Complex Tissues

The development of single-cell omics tools has enabled scientists to study the tumor microenvironment (TME) in unprecedented detail. However, each of the different techniques may have its unique strengths and limitations. Here we directly compared two commercially available high-throughput single-cell RNA sequencing (scRNA-seq) technologies - droplet-based 10X Chromium vs. microwell-based BD Rhapsody - using paired samples from patients with localized prostate cancer (PCa) undergoing a radical prostatectomy. Although high technical consistency was observed in unraveling the whole transcriptome, the relative abundance of cell populations differed. Cells with low-mRNA content such as T cells were underrepresented in the droplet-based system, at least partly due to lower RNA capture rates. In contrast, microwell based scRNA-seq recovered less cells of epithelial origin. Moreover, we discovered platform-dependent variabilities in mRNA quantification and cell-type marker annotation. Overall, our study provides important information for selection of the appropriate scRNA-seq platform and for the interpretation of published results. SYNOPSISO_LIComparison of scRNA-seq protocols uncovers disparities in RNA-to-library conversion C_LIO_LIMicrowell-based scRNA-seq technology excels in capturing low-mRNA content cells C_LIO_LIBiased transcriptomes due to gene specific RNA detection efficacies by both platforms C_LIO_LIThe study guides in informed scRNA-seq platform selection and data interpretation C_LI

cancer biology↗

bioRxiv2022

Functional precision profiling reveals non-mutational rewiring of kinase signaling networks in colorectal cancer

BackgroundDespite major advances in the development of targeted therapies, precision (immuno)oncology approaches for patients with colorectal cancer continue to lag behind other solid cancers. Functional precision oncology - a strategy that is based on perturbing primary tumor cells from cancer patients with drugs - could provide an alternate road forward to personalize treatment. MethodsWe extend here the functional precision oncology paradigm to measuring phosphoproteome landscapes using patient-derived organoids (PDOs). We first employed steady-state multi-omics (exome sequencing, RNA sequencing, and proteomics) and single-cell characterization of the PDOs. The PDOs were then perturbed with kinase inhibitors (MEKi, PI3Ki, mTORi, TBKi, BRAFi, and TAKi), and large-scale phosphoproteomics profiling using data-independent acquisition was carried out. Further, we used imaging mass-cytometry-based single-cell proteomic profiling of the primary tumors to characterize cellular composition of the tumor-microenvironment (TME) and to quantify heterocellular signaling crosstalk. ResultsWe show that kinase inhibitors induce profound off-target effects resulting in a crosstalk with oncogenic and immune-related pathways. Reconstruction of the topologies of the kinase networks revealed that the patient-specific rewiring of the central EGFR-RAS-MAPK network is unaffected by mutations. Moreover, we show non-genetic heterogeneity of the PDOs and patient- and inhibitor-specific upregulation of stemness and differentiation genes by kinase inhibitors. We complemented our functional profiling by spatial proteomics profiling of the primary tumors using imaging mass cytometry. We quantify spatial heterocellular crosstalk and tumor-immune cell interactions, showing an avoidance of PD1+ immune cells and PD-L1+ tumor cells. ConclusionsCollectively, we provide a multi-modal framework for inferring tumor cell intrinsic signaling and external signaling from the TME to inform precision (immuno)-oncology in colorectal cancer.

cancer biology↗

bioRxiv2022

The Solanum americanum pangenome and effectoromics reveal new resistance genes against potato late blight

Late blight caused by the oomycete pathogen Phytophthora infestans continues to cause major worldwide losses in potato and tomato. Most accessions of Solanum americanum, a globally distributed, wild Solanaceae plant, are highly resistant to late blight. We generated high-quality reference genomes of four S. americanum accessions, re-sequenced 52 accessions, and we defined variation in the NLR immune receptor genes (the S. americanum NLRome). We further screened for variation in recognition of [~]315 P. infestans RXLR effectors in 52 S. americanum accessions. Using these genotypic and phenotypic data, we cloned three novel NLR-encoding genes Rpi-amr4, Rpi-amr16 and Rpi-amr17, and determined their corresponding RXLR effector genes Avramr4 (PITG_22825), Avramr16 (PITG_02860) and Avramr17 (PITG_04373) from P. infestans. These genomic resources and methodology will support efforts to convert potato into a "nonhost" of late blight and can be applied to diseases of other crops.

plant biology↗