PhyDOSE: Design of follow-up single-cell sequencing experiments of tumors

by Leah L. Weber, Nuraini Aguse, Nicholas Chia, Mohammed El-Kebir The combination of bulk and single-cell DNA sequencing data of the same tumor enables the inference of high-fidelity phylogenies that form the input to many important downstream analyses in cancer genomics. While many studies simultaneously perform bulk and single-cell sequencing, some studies hav e analyzed initial bulk data to identify which mutations to target in a follow-up single-cell sequencing experiment, thereby decreasing cost. Bulk data provide an additional untapped source of valuable information, composed of candidate phylogenies and associated clonal prevalence. Here, we introduc e PhyDOSE, a method that uses this information to strategically optimize the design of follow-up single cell experiments. Underpinning our method is the observation that only a small number of clones uniquely distinguish one candidate tree from all other trees. We incorporate distinguishing features into a probabilistic model that infers the number of cells to sequence so as to confidently reconstruct the phylogeny of the tumor. We validate PhyDOSE using simulations and a retrospective analysis of a leukemia patient, concluding that PhyDOSE’s computed number of cells resolves tree ambiguity even in the presence of typical single-cell sequencing errors. We also conduct a retrospective analysis on an acute myeloid leukemia cohort, demonstrating the potential to achieve similar results with a significant reduction in t...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research

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Conclusions: In summary, the dominant function of FAS may vary in different malignancies. FAS mRNA expression was correlated with better OS in breast cancer, gastric cancer and lung cancer, but worse OS in pancreatic cancer and AML. We also suggested that FAS mRNA expression could be a potential biomarker for cabozantinib and erlotinib.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
In this study, we found that NiPT triggered autophagy both in vitro and in vivo. Mechanistically, NiPT targets two DUBs, USP14, and UCHL5, and increased the total cellular level of polyubiquitination. Deletion of the Ubiquitin Associated (UBA) domain of P62 that is required for polyubiquitin binding prevented NiPT-induced autophagy. NiPT-induced autophagy is through either concomitant activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR) signaling, or eliciting endoplasmic reticulum (ER)-stress by activating activating transcription factor 4 (ATF4) and C/EBP-homologous p...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Basel, 23 March 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the phase III VIALE-A study met its dual primary endpoints of overall survival and composite complete remission rate (CR + CRi). Venclexta ®/Venclyxto® (venetoclax) in combination with azacitidine, a hypomethylating agent, showed a statistically significant improvement in overall survival in people with previously untreated acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy, compared to azacitidine alone. Safety for Venclexta/Venclyxto plus azacitidine appeared consistent with the known safety profile ...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
ConclusionLiposomal formulations are less toxic than drugs alone and have better pharmacological parameters. Although they seem to be the first choice for drug delivery systems for various diseases, further research about dosage regimen regarding dose and time needs to be carried out.
Source: Cancer Nanotechnology - Category: Cancer & Oncology Source Type: research
Conclusions: The 5-year OS of patients with stage III NSCLC treated with CRT was in keeping with survival figures reported from prospective clinical trials. There is, however, significant morbidity associated with long-term survival and this should be taken into account when making informed treatment decisions. PMID: 31737309 [PubMed]
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Tags: J Thorac Dis Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
In this study, we treated NSCLC cell lines A549 and H460 and a normal lung cell line, 16HBE, with LukS-PV and investigated the biological roles of LukS-PV in NSCLC. Cells were treated with varying concentrations of LukS-PV and cell viability was evaluated by CCK8 and EdU assay. Flow cytometry was used to detect cell apoptosis and analyze the cell cycle, and the expression of apoptosis and cell cycle-associated proteins and genes were identified by western blotting analysis and qRT-polymerase chain reaction, respectively. We found that LukS-PV inhibited the proliferation of NSCLC cells but had little cytotoxicity in normal ...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Growing evidence has demonstrated that epigenetic dysregulation is a common pathological feature in human cancer cells. Global alterations in the epigenetic landscape are prevalent in malignant cells across different solid tumours including, prostate cancer, non-small-cell lung cancer, renal cell carcinoma, and in haemopoietic malignancy. In particular, DNA hypomethylation and histone hypoacetylation have been observed in acute myeloid leukaemia (AML) patient blasts, with histone methylation being an emerging area of study. Histone 3 lysine 9 trimethylation (H3K9me3) is a post-translational modification known to be invol...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
The objective of this study was to develop a population-pharmacokinetic model of durvalumab in patients with various hematologic malignancies and to investigate the effects of demographic and disease factors on the pharmacokinetics in this population.MethodsA total of 1812 concentrations from 267 patients with myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma were included in the analysis.ResultsThe pharmacokinetics of durvalumab was adequately described by a two-compartment model with first-order elimination. A decrease in durvalumab clearance over time was main...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research
The objective of this study was to develop a population-pharmacokinetic model of durvalumab in patients with various hematologic malignancies and to investigate the effects of demographic and disease factors on the pharmacokinetics in this population. METHODS: A total of 1812 concentrations from 267 patients with myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma were included in the analysis. RESULTS: The pharmacokinetics of durvalumab was adequately described by a two-compartment model with first-order elimination. A decrease in durvalumab clearance ov...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Pharmacokinet Source Type: research
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