Shaolong Cao's research while affiliated with University of Texas MD Anderson Cancer Center and other places

Publications (38)

Article
Full-text available
[This corrects the article DOI: 10.1016/j.isci.2022.104551.].
Article
Resistance to androgen receptor-targeted therapy due to tumor heterogeneity and clonal evolution is a key challenge for improving prostate cancer outcomes. Despite this, the transcriptomic and chromatin accessibility changes contributing to the emergence of resistance remain incompletely understood at the level of individual cells. Using single-cel...
Article
Full-text available
Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into ac...
Article
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Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of...
Preprint
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Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, differences in tumor cell total mRNA content have not been comprehensively assessed. Technical and analytical challenges have impeded examination of total mRNA expression at scale across cancers. To address this, we developed a model for quan...
Preprint
Full-text available
We used whole-organ mapping to study loco-geographic molecular changes in evolution of human bladder cancer from mucosal field effects. The integrative multi-platform analyses based on genome-wide RNA sequencing, methylation, copy number variations, and whole exome sequencing identified over 100 dysregulated canonical pathways involving immunity, t...
Preprint
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Subpopulations of tumor cells characterized by mutation profiles may confer differential fitness and consequently influence prognosis of cancers. Understanding subclonal architecture has the potential to provide biological insight in tumor evolution and advance precision cancer treatment. Recent methods comprehensively integrate single nucleotide v...
Preprint
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Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. We employed single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and tr...
Article
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Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all...
Preprint
Prostate cancer is profoundly heterogeneous and patients would benefit from methods that stratify clinically indolent from more aggressive forms of the disease. We employed single-cell assay for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified...
Preprint
Full-text available
Cancers can vary greatly in their transcriptomes. In contrast to alterations in specific genes or pathways, the significance of differences in tumor cell total mRNA content is poorly understood. Studies using single-cell sequencing or model systems have suggested a role for total mRNA content in regulating cellular phenotypes. However, analytical c...
Conference Paper
Background: At present, conventional clinical and histopathological evaluations are not sufficient to distinguish biologically indolent cancers from those that will exhibit aggressive behavior. We hypothesize that global transcriptomic activity of tumor cells reflects the end cumulative result of somatic, germline, and epigenetic alterations, as we...
Article
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Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatri...
Article
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The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories...
Article
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We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silic...
Article
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Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG...
Article
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Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Ge...
Conference Paper
Background: Most tumor samples consist of a variable proportion of malignant and nonmalignant cells including epithelial cells, fibroblasts, and infiltrating immune cells, which confounds biomarker studies of response to treatment. Deconvolution approaches have been developed for transcriptomes to address this heterogeneity in tumor samples. The Ca...
Preprint
Full-text available
The deconvolution of transcriptomic data from heterogeneous tissues in cancer studies remains challenging. Available software faces difficulties for accurately estimating both component-specific proportions and expression profiles for individual samples. To address these challenges, we present a new R-implementation pipeline for the more accurate a...
Data
P-values are calculated for differential test (Benjamini-Hochberg correction) of deconvolved expression for immune component versus stromal component, and immune component versus tumor component, respectively, related to Figure 4.
Data
Document S1. Transparent Methods, Figures S1–S15, and Tables S1–S9
Article
Full-text available
Transcriptome deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions and expression profiles for individual samples. We present DeMixT, a new tool to deconvolve high-dimensional data from mixtures of more than two components. DeMixT implements a...
Article
Full-text available
We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous de...
Preprint
Full-text available
Transcriptomic deconvolution in cancer and other heterogeneous tissues remains challenging. Available methods lack the ability to estimate both component-specific proportions and expression profiles for individual samples. We present DeMixT , a new tool to deconvolve high dimensional data from mixtures of more than two components. DeMixT implements...

Citations

... Here, we address this need through the creation of the Cancer LncRNA Census 2 (CLC2). It not only extends our previous CLC dataset by several fold (42), but more importantly, CLC2 takes a major step forward methodologically, by implementing an automated curation component that utilizes functional evolutionary conservation for the first time. Using these data, we present a comprehensive analysis of the genomic and clinical features of cancer lncRNAs. ...
... The auto-encoder-enabled technique is advised by these days [10,11,12,13,14,15,16] for cancer prediction in the clinical environment with fixed lung and skin tumors. In cancer cases, almost all the feature extraction is in picture format and based on biopsy and other techniques used in the system's laboratories. ...
... The ICMandTE hemi-embryo was composed of both trophoblast and inner cell mass in unknown relative proportions. In order to estimate the relative gene expression of both cell types, the DeMixT R package version 1.4.0 was used [38,39]. Starting from a dataset obtained from one cell type, DeMixT estimates the proportion of cells in the mixed samples and performs a deconvolution algorithm on gene expression. ...
... . In addition to known mutation-activated oncogenic signalling pathways [4], recent attention has focused on a potential oncogenic role for the neurotrophin receptor tropomyosin-related tyrosine kinase A (TrkA) in CMM. TrkA mediates melanocyte and melanoma cell responses to neurotrophic factors [5,6], the gene that encodes TrkA, NTRK1, is frequently amplified in CMMs, increased TrkA expression and intracellular activation have been positively correlated with CMM progression and poor outcome [7][8][9][10] and TrkA fusion oncogenes have been detected in CMMs and spitzoid melanomas [11,12]. ...
... Recently, He et al. showed that in CRPC cell lines resistant to enzalutamide, AR is recruited to the chromatin, even in regions lacking canonical androgen-responsive elements [210]. Using both bulk and single cell chromatin accessibility data in models of enzalutamide resistance, we have recently shown that enzalutamide resistance is associated with chromatin relaxation and reprogrammed accessibility [211], which is consistent with potential alterations of TF binding in these cells, including the reprogramming of AR binding. ...
... Multiple methods have been developed to estimate cell fractions [58][59][60][61] , including some that aim to reconstruct the cancer-specific transcriptome from a cell mixture 62,63 . Another level of complexity is that cancer cells themselves often consist of multiple clones and lineages that may exhibit heterogeneous traits not visible in a bulk transcriptomics measurement. ...
... After filtering out all genes with at least 3 null count values in at least one group (ON or OM) per hemi-195 embryo (ICMandTE or TE_part), removing genes with a null variance in TE_part and adding the value 196 "1" to all count values in ICMandTE and TE_part datasets, deconvolution was performed using the 197 DeMixT R package version 1.4.0 [50,51]. Output datasets were DeMixT_ICM_cells and 198 DeMixT_TE_cells, corresponding to the deconvoluted gene expression in ICM cells and TE cells of 199 ICMandTE, respectively. ...
... Generally, a high level of genomic instability highlights the potential of generating neoantigens or neo-epitopes to be applied in immunotherapies. However, it is difficult to find suitable neoantigens in osteosarcoma, due to few of the genomic alterations ultimately expressed as neoantigens ( [43]). Moreover, most of the antigens expressed in ...
... About work for future improvements, we plan to improve the function of WAVECNV and open the input of some optional parameters so that users can more flexibly control the precision of CNV-detection results [26]. We will use additional information from the sequencing data, such as variant allele frequency (VAF) [27,28], to more accurately estimate tumor purity and absolute copy number. In addition, we will develop a multi-sample CNV-detection method of WAVECNV to study the changes in the absolute copy number of genes in cancer patients at different periods [9] and lay a solid foundation for the inference of tumor subclonal populations. ...
... The relative contributions of these different processes can be quantified by algorithms that assign an activity (or exposure) to each detected mutational signature [4]. Recent work [5,6,7] has revealed that i) these activities vary during cancer development (i.e., tumor progression) in a cancer-type-specific way and ii) many mutational signatures are primarily active only in either early-or late-tumor progression [5,6]. We have previously described the method TrackSig [7], which uses optimal segmentation to segment an evolutionary trajectory defined by inferred cancer cell fraction (CCF). ...