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Abstract BackgroundComputational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell RNA-seq data to create simulated pseudobulk datasets by adding individual cells-types in controlled proportions. ResultsIn our work, we show that the standard application of this approach, which uses randomly selected single cells, regardless of the intrinsic difference between them, generates synthetic bulk expression values that lack appropriate biological variance. We demonstrate why and how the current bulk simulation pipeline with random cells is unrealistic and propose a heterogeneous simulation strategy as a solution. The heterogeneously simulated bulk samples match up with the variance observed in real bulk datasets and therefore provide concrete benefits for benchmarking in several ways. We demonstrate that conceptual classes of deconvolution methods differ dramatically in their robustness to heterogeneity with reference-free methods performing particularly poorly. For regression-based methods, the heterogeneous simulation provides an explicit framework to disentangle the contributions of reference construction and regression methods to performance. Finally, we perform an extensive benchmark of diverse methods across eight different datasets and find BayesPrism and a hybrid MuSiC/CIBERSORTx approach to be the top performers. ConclusionsOur heterogeneous bulk simulation method and the entire benchmarking framework is implemented in a user friendly packagehttps://github.com/humengying0907/deconvBenchmarkingandhttps://doi.org/10.5281/zenodo.8206516, enabling further developments in deconvolution methods.
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Non‐linear phylogenetic regression using regularised kernels
Abstract Phylogenetic regression is a type of generalised least squares (GLS) method that incorporates a modelled covariance matrix based on the evolutionary relationships between species (i.e. phylogenetic relationships). While this method has found widespread use in hypothesis testing via phylogenetic comparative methods, such as phylogenetic ANOVA, its ability to account for non‐linear relationships has received little attention.To address this, here we implement a phylogenetic Kernel Ridge Regression (phyloKRR) method that utilises GLS in a high‐dimensional feature space, employing linear combinations of phylogenetically weighted data to account for non‐linearity. We analysed two biological datasets using the Radial Basis Function and linear kernel function. The first dataset contained morphometric data, while the second dataset comprised discrete trait data and diversification rates as response variable. Hyperparameter tuning of the model was achieved through cross‐validation rounds in the training set.In the tested biological datasets, phyloKRR reduced the error rate (as measured by RMSE) by around 20% compared to linear‐based regression when data did not exhibit linear relationships. In simulated datasets, the error rate decreased almost exponentially with the level of non‐linearity.These results show that introducing kernels into phylogenetic regression analysis presents a novel and promising tool for complementing phylogenetic comparative methods. We have integrated this method into Python package named phyloKRR, which is freely available at:https://github.com/ulises‐rosas/phylokrr.
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- Award ID(s):
- 2225130
- PAR ID:
- 10531246
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Methods in Ecology and Evolution
- Volume:
- 15
- Issue:
- 9
- ISSN:
- 2041-210X
- Format(s):
- Medium: X Size: p. 1611-1623
- Size(s):
- p. 1611-1623
- Sponsoring Org:
- National Science Foundation
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