Biology subjects

Canoll, P.

Publications and source records attributed to Canoll, P..

3 recordsLinked to original sources

bioRxiv2018

De novo Gene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization

Common approaches to gene signature discovery in single cell RNA-sequencing (scRNA-seq) depend upon predefined structures like clusters or pseudo-temporal order, require prior normalization, or do not account for the sparsity of single cell data. We present single cell Hierarchical Poisson Factorization (scHPF), a Bayesian factorization method that adapts Hierarchical Poisson Factorization [1] for de novo discovery of both continuous and discrete expression patterns from scRNA-seq. scHPF does not require prior normalization and captures statistical properties of single cell data better than other methods in benchmark datasets. Applied to scRNA-seq of the core and margin of a high-grade glioma, scHPF uncovers marked differences in the abundance of glioma subpopulations across tumor regions and subtle, regionally-associated expression biases within glioma subpopulations. scHFP revealed an expression signature that was spatially biased towards the glioma-infiltrated margins and associated with inferior survival in glioblastoma.

systems biology↗

bioRxiv2018

Connecting Patterns of Tumor Growth with Sex Differences in Extreme Survivorship for Primary Glioblastoma Patients

BackgroundSex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences.\n\nMethodsCombining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients. Pretreatment MR images of 494 glioblastoma patients (299 males and 195 females) were segmented to quantify tumor volumes. Cox proportional hazard (CPH) models and Students t-tests were used to assess which variables were associated with survival outcomes.\n\nResultsAmong males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival.\n\nConclusionDespite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes, which emphasizes the importance of considering sex as a biological factor when determining patient prognosis and treatment approach.

cancer biology↗

bioRxiv2018

Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma

BackgroundDespite extensive molecular characterization, we lack a comprehensive understanding of lineage identity, differentiation, and proliferation in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq.\n\nResultsWhile HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, reminiscent of molecular interactions between glioma and immune cells established in animal models. Additionally, we discovered a tight coupling between lineage resemblance and proliferation among malignantly transformed cells. Glioma cells that resemble oligodendrocyte progenitors, which proliferate in the brain, are often found in the cell cycle. Conversely, glioma cells that resemble astrocytes, neuroblasts, and oligodendrocytes, which are non-proliferative in the brain, are generally non-cycling in tumors.\n\nConclusionsThese studies reveal a relationship between cellular identity and proliferation in HGG and distinct population structures that reflects the extent of neural and non-neural lineage resemblance among malignantly transformed cells.

cancer biology↗