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Register a new userComparative Analysis of Packages and Algorithms for the Analysis of Spatially Resolved Transcriptomics Data
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The technology to generate Spatially Resolved Transcriptomics (SRT) data is rapidly being improved and applied to investigate a variety of biological tissues. The ability to interrogate how spatially localised gene expression can lend new insight to different tissue development is critical, but the appropriate tools to analyse this data are still emerging. This chapter reviews available packages and pipelines for the analysis of different SRT datasets with a focus on identifying spatially variable genes (SVGs) alongside other aims, while discussing the importance of and challenges in establishing a standardised ground truth in the biological data for benchmarking.
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Data from discovery proteomic and phosphoproteomic experiments typically include missing values that correspond to proteins that have not been identified in the analyzed sample. Replacing the missing values with random numbers, a process known as imputation, avoids apparent infinite fold-change values. However, the procedure comes at a cost: Imputing a large number of missing values has the potential to significantly impact the results of the subsequent differential expression analysis. We propose a method that identifies differentially expressed proteins by ranking their observed changes with respect to the changes observed for other proteins. Missing values are taken into account by this method directly, without the need to impute them. We illustrate the performance of the new method on two distinct datasets and show that it is robust to missing values and, at the same time, provides results that are otherwise similar to those obtained with edgeR which is a state-of-art differential expression analysis method. The new method for the differential expression analysis of proteomic data is available as an easy to use Python package.
Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequently employed to pool local results. However, if class labels are inhomogeneously distributed between cohorts, their accuracy may drop. Flimma (https://exbio.wzw.tum.de/flimma/) addresses this issue by implementing the state-of-the-art workflow limma voom in a privacy-preserving manner, i.e. patient data never leaves its source site. Flimma results are identical to those generated by limma voom on combined datasets even in imbalanced scenarios where meta-analysis approaches fail.
Motivation: We introduce TRONCO (TRanslational ONCOlogy), an open-source R package that implements the state-of-the-art algorithms for the inference of cancer progression models from (epi)genomic mutational profiles. TRONCO can be used to extract population-level models describing the trends of accumulation of alterations in a cohort of cross-sectional samples, e.g., retrieved from publicly available databases, and individual-level models that reveal the clonal evolutionary history in single cancer patients, when multiple samples, e.g., multiple biopsies or single-cell sequencing data, are available. The resulting models can provide key hints in uncovering the evolutionary trajectories of cancer, especially for precision medicine or personalized therapy. Availability: TRONCO is released under the GPL license, it is hosted in the Software section at http://bimib.disco.unimib.it/ and archived also at bioconductor.org. Contact: [email protected]
Recent technology breakthrough in spatial molecular profiling has enabled the comprehensive molecular characterizations of single cells while preserving spatial information. It provides new opportunities to delineate how cells from different origins form tissues with distinctive structures and functions. One immediate question in analysis of spatial molecular profiling data is how to identify spatially variable genes. Most of the current methods build upon the geostatistical model with a Gaussian process that relies on selecting ad hoc kernels to account for spatial expression patterns. To overcome this potential challenge and capture more types of spatial patterns, we introduce a Bayesian approach to identify spatially variable genes via Ising model. The key idea is to use the energy interaction parameter of the Ising model to characterize spatial expression patterns. We use auxiliary variable Markov chain Monte Carlo algorithms to sample from the posterior distribution with an intractable normalizing constant in the Ising model. Simulation results show that our energy-based modeling approach led to higher accuracy in detecting spatially variable genes than those kernel-based methods. Applying our method to two real spatial transcriptomics datasets, we discovered novel spatial patterns that shed light on the biological mechanisms. The proposed method presents a new perspective for analyzing spatial transcriptomics data.
Genomic data sets are growing dramatically as the cost of sequencing continues to decline and small sequencing devices become available. Enormous community databases store and share this data with the research community, but some of these genomic data analysis problems require large scale computational platforms to meet both the memory and computational requirements. These applications differ from scientific simulations that dominate the workload on high end parallel systems today and place different requirements on programming support, software libraries, and parallel architectural design. For example, they involve irregular communication patterns such as asynchronous updates to shared data structures. We consider several problems in high performance genomics analysis, including alignment, profiling, clustering, and assembly for both single genomes and metagenomes. We identify some of the common computational patterns or motifs that help inform parallelization strategies and compare our motifs to some of the established lists, arguing that at least two key patterns, sorting and hashing, are missing.
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