DNA microarrays have been widely applied to the study of human cancer, delineating myriad molecular subtypes of cancer, many of which are associated with distinct biological underpinnings, disease progression and treatment response. These primary analyses have begun to decipher the molecular heterogeneity of cancer, but integrative analyses that evaluate cancer transcriptome data in the context of other data sources are often capable of extracting deeper biological insight from the data. Here we discuss several such integrative computational and analytical approaches, including meta-analysis, functional enrichment analysis, interactome analysis, transcriptional network analysis and integrative model system analysis.
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http://dx.doi.org/10.1038/ng1570 | DOI Listing |
Clin Cancer Res
January 2025
The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Background: KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration.
Methods: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included in the analysis. Pre-treatment NGS data were collected per protocol.
Am J Cancer Res
December 2024
School of Basic Medical Sciences, Jiamusi University No. 258, Xuefu Street, Xiangyang District, Jiamusi 154007, Heilongjiang, China.
Breast cancer is the most common malignant tumour in women, with more than 685,000 women dying of breast cancer each year. The heterogeneity of breast cancer complicates both treatment and diagnosis. Traditional methods based on histopathology and hormone receptor status are now no longer sufficient.
View Article and Find Full Text PDFUnlabelled: Quantitative understanding of mitochondrial heterogeneity is necessary for elucidating the precise role of these multifaceted organelles in tumor cell development. We demonstrate an early mechanistic role of mitochondria in initiating neoplasticity by performing quantitative analyses of structure-function of single mitochondrial components coupled with single cell transcriptomics. We demonstrate that the large Hyperfused-Mitochondrial-Networks (HMNs) of keratinocytes promptly get converted to the heterogenous Small-Mitochondrial-Networks (SMNs) as the stem cell enriching dose of the model carcinogen, TCDD, depolarizes mitochondria.
View Article and Find Full Text PDFComputerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules.
View Article and Find Full Text PDFGene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
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