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Tyekucheva, S.

Publications and source records attributed to Tyekucheva, S..

5 recordsLinked to original sources

KODAMA enables self-guided weakly supervised learning in spatial transcriptomics

Spatial transcriptomics provides researchers with a powerful tool to investigate gene expression patterns within their native positional context in tissues, revealing intricate cellular relationships. However, analyzing spatial transcriptomics data presents unique challenges due to their high dimensionality and complexity. Several competitive tools have emerged, each aiming to integrate spatial dependencies into their workflow. Yet, the overall performance of these approaches remains constrained by limitations in prediction accuracy and compatibility with specific data types. Here, we introduce the third version of the KODAMA algorithm, specifically tailored for spatial transcriptomics analysis. This upgraded version incorporates a novel approach that effectively reduces data dimensionality while preserving spatial information. At its core, the KODAMA algorithm employs parallel iterations that enforce spatial constraints throughout an embedded clustering process. Our method provides the flexibility to simultaneously analyze multiple samples, streamlining analysis workflows. Additionally, it extends beyond traditional 2D analysis to accommodate multidimensional datasets, including 3D spatial information. KODAMA seamlessly integrates into various pipelines, such as Seurat and Giotto. Extensive evaluations of KODAMA on 10x Visium, Visium HD, and image-based 3D datasets demonstrate its high accuracy in spatial domain prediction. Comparative analyses against alternative dimensionality reduction techniques and spatial analysis tools consistently validate and highlight KODAMAs superior performance in unraveling the spatial organization of cellular components across both single and integrated tissue samples.

bioinformatics↗

curatedPCaData: Integration of clinical, genomic, and signature features in a curated and harmonized prostate cancer data resource

Genomic and transcriptomic data have been generated across a wide range of prostate cancer (PCa) study cohorts. These data can be used to better characterize the molecular features associated with clinical outcomes and to test hypotheses across multiple, independent patient cohorts. In addition, derived features, such as estimates of cell composition, risk scores, and androgen receptor (AR) scores, can be used to develop novel hypotheses leveraging existing multi-omic datasets. The full potential of such data is yet to be realized as independent datasets exist in different repositories, have been processed using different pipelines, and derived and clinical features are often not provided or unstandardized. Here, we present the curatedPCaData R package, a harmonized data resource representing >2900 primary tumor, >200 normal tissue, and >500 metastatic PCa samples across 19 datasets processed using standardized pipelines with updated gene annotations. We show that meta-analysis across harmonized studies has great potential for robust and clinically meaningful insights. curatedPCaData is an open and accessible community resource with code made available for reproducibility.

bioinformatics↗

Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays

Tissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1,448 primary prostate cancers. In half of the biomarkers, more than 10% of biomarker variance was attributable to between-TMA differences (range, 1-48%). We implemented different methods to mitigate batch effects (R package batchtma), tested in plasmode simulation. Biomarker levels were more similar between mitigation approaches compared to uncorrected values. For some biomarkers, associations with clinical features changed substantially after addressing batch effects. Batch effects and resulting bias are not an error of an individual study but an inherent feature of TMA-based protein biomarker studies. They always need to be considered during study design and addressed analytically in studies using more than one TMA.

pathology↗

Transcriptional landscape of PTEN loss in primary prostate cancer

PTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature of PTEN loss, while also accounting for potential confounders due to ERG rearrangements. Strikingly, the signature indicates a strong activation of both innate and adaptive immune systems upon PTEN loss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape of PTEN loss in PCa that comprises both the coding and an extensive non-coding counterpart.

cancer biology↗

Transcriptome Deconvolution of Heterogeneous Tumor Samples with Immune Infiltration

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 an iterated conditional mode algorithm and a novel gene-set-based component merging approach to improve accuracy. In a series of experimental validation studies and application to TCGA data, DeMixT showed high accuracy. Improved deconvolution is an important step towards linking tumor transcriptomic data with clinical outcomes. An R package, scripts and data are available: https://github.com/wwylab/DeMixT/.

bioinformatics↗