Biology subjects

Lahdesmaki, H.

Publications and source records attributed to Lahdesmaki, H..

4 recordsLinked to original sources

bioRxiv2023

DeconV: Probabilistic Cell Type Deconvolution from Bulk RNA-sequencing Data

Bulk RNA-Seq remains a widely adopted technique to profile gene expression, primarily due to the persistent challenges associated with achieving single-cell resolution. However, a key challenge is accurately estimating the proportions of different cell types within these bulk samples. To address this issue, we introduce DeconV, a probabilistic framework for cell-type deconvolution that uses scRNA-Seq data as a reference. This approach aims to mitigate some of the limitations in existing methods by incorporating statistical frameworks developed for scRNA-Seq, thereby simplifying issues related to reference preprocessing such as normalization and marker gene selection. We benchmarked DeconV against established methods, including MuSiC, CIBERSORTx, and Scaden. Our results show that DeconV performs comparably in terms of accuracy to the best-performing method, Scaden, but provides additional interpretability by offering confidence intervals for its predictions. Furthermore, the modular design of DeconV allows for the investigation of discrepancies between bulk-sequenced samples and artificially generated pseudo-bulk samples.

bioinformatics↗

bioRxiv2021

Scalable estimation of microbial co-occurrence networks with Variational Autoencoders

Estimating microbe-microbe interactions is critical for understanding the ecological laws governing microbial communities. Rapidly decreasing sequencing costs have promised new opportunities to estimate microbe-microbe interactions across thousands of uncultured, unknown microbes. However, typical microbiome datasets are very high dimensional and accurate estimation of microbial correlations requires tens of thousands of samples, exceeding the computational capabilities of existing methodologies. Furthermore, the vast majority of microbiome studies collect compositional metagenomics data which enforces a negative bias when computing microbe-microbe correlations. The Multinomial Logistic Normal (MLN) distribution has been shown to be effective at inferring microbe-microbe correlations, however scalable Bayesian inference of these distributions has remained elusive. Here, we show that carefully constructed Variational Autoencoders (VAEs) augmented with the Isometric Log-ratio (ILR) transform can estimate low-rank MLN distributions thousands of times faster than existing methods. These VAEs can be trained on tens of thousands of samples, enabling co-occurrence inference across tens of thousands of microbes without regularization. The latent embedding distances computed from these VAEs are competitive with existing beta-diversity methods across a variety of mouse and human microbiome classification and regression tasks, with notable improvements on longitudinal studies.

bioinformatics↗

bioRxiv2018

Data-driven multiscale modeling reveals the role of metabolic coupling for the spatio-temporal growth dynamics of yeast colonies

MotivationMulticellular entities, such as mammalian tissues or microbial biofilms, typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding on how cell-cell and metabolic coupling produce functionally optimized structures is still limited.\n\nResultsHere, we present a data-driven spatial framework to computationally investigate the development of one multicellular structure, yeast colonies. Using experimental growth data from homogeneous liquid media conditions, we develop and parameterize a dynamic cell state and growth model. We then use the resulting model in a coarse-grained spatial model, which we calibrate using experimental time-course data of colony growth. Throughout the model development process, we use state-of-the-art statistical techniques to handle the uncertainty of model structure and parameterization. Further, we validate the model predictions against independent experimental data and illustrate how metabolic coupling plays a central role in colony formation.\n\nAvailabilityExperimental data and a computational implementation to reproduce the results are available at http://research.cs.aalto.fi/csb/software/multiscale/code.zip.\n\nContactjukka.intosalmi@aalto.fi, alexander.skupin@uni.lu

bioinformatics↗

bioRxiv2018

SCHiRM: Single Cell Hierarchical Regression Model to detect dependencies in read count data

MotivationModern single cell RNA sequencing (scRNA-seq) technologies have made it possible to measure the RNA content of individual cells. The scRNA-seq data provide us with detailed information about the cellular states but, despite several pioneering efforts, it remains an open research question how regulatory networks could be inferred from these noisy discrete read count data.\n\nResultsHere, we introduce a hierarchical regression model which is designed for detecting dependencies in scRNA-seq and other count data. We model count data using the Poisson-log normal distribution and, by means of our hierarchical formulation, detect the dependencies between genes using linear regression model for the latent, cell-specific gene expression rate parameters. The hierarchical formulation allows us to model count data without artificial data transformations and makes it possible to incorporate normalization information directly into the latent layer of the model. We test the proposed approach using both simulated and experimental data. Our results show that the proposed approach performs better than standard regression techniques in parameter inference task as well as in variable selection task.\n\nAvailabilityAn implementation of the method is available at https://github.com/jeintos/SCHiRM.\n\nContactjukka.intosalmi@aalto.fi, harri.lahdesmaki@aalto.fi

bioinformatics↗