Biology subjects

Altenbuchinger, M.

Publications and source records attributed to Altenbuchinger, M..

3 recordsLinked to original sources

bioRxiv2023

Adaptive Digital Tissue Deconvolution

MotivationThe inference of cellular compositions from bulk and spatial transcriptomics data increasingly complements data analyses. Multiple computational approaches were suggested and recently, machine learning techniques were developed to systematically improve estimates. Such approaches allow to infer additional, less abundant cell types. However, they rely on training data which do not capture the full biological diversity encountered in transcriptomics analyses; data can contain cellular contributions not seen in the training data and as such, analyses can be biased or blurred. Thus, computational approaches have to deal with unknown, hidden contributions. Moreover, most methods are based on cellular archetypes which serve as a reference; e.g., a generic T-cell profile is used to infer the proportion of T-cells. It is well known that cells adapt their molecular phenotype to the environment and that pre-specified cell archetypes can distort the inference of cellular compositions. ResultsWe propose Adaptive Digital Tissue Deconvolution (ADTD) to estimate cellular proportions of pre-selected cell types together with possibly unknown and hidden background contributions. Moreover, ADTD adapts prototypic reference profiles to the molecular environment of the cells, which further resolves cell-type specific gene regulation from bulk transcriptomics data. We verify this in simulation studies and demonstrate that ADTD improves existing approaches in estimating cellular compositions. In an application to bulk transcriptomics data from breast cancer patients, we demonstrate that ADTD provides insights into cell-type specific molecular differences between breast cancer subtypes. Availability and implementationA python implementation of ADTD and a tutorial are available at Gitlab and zenodo (doi:10.5281/zenodo.7548362). Contactmichael.altenbuchinger@bioinf.med.uni-goettingen.de and sushma.grellscheid@uib.no Supplementary informationSupplementary material is available at Bioinformatics online.

bioinformatics↗

bioRxiv2022

SpaCeNet: Spatial Cellular Networks from omics data

Advances in omics technologies have allowed spatially resolved molecular profiling of single cells, providing a window not only into the diversity and distribution of cell types within a tissue, but also into the effects of interactions between cells in shaping the transcriptional landscape. Cells send chemical and mechanical signals which are received by other cells, where they can subsequently initiate context-specific gene regulatory responses. These interactions and their responses shape the individual molecular phenotype of a cell in a given microenvironment. RNAs or proteins measured in individual cells together with the cells spatial distribution provide invaluable information about these mechanisms and the regulation of genes beyond processes occurring independently in each individual cell. "SpaCeNet" is a method designed to elucidate both the intracellular molecular networks (how molecular variables affect each other within the cell) and the intercellular molecular networks (how cells affect molecular variables in their neighbors). This is achieved by estimating conditional independence relations between captured variables within individual cells and by disentangling these from conditional independence relations between variables of different cells. A python implementation of SpaCeNet is publicly available at https://github.com/sschrod/SpaCeNet.

bioinformatics↗

bioRxiv2022

The Network Zoo: a multilingual package for the inference and analysis of biological networks

Inference and analysis of cellular biological networks requires software tools that integrate multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is an open-source software suite to model biological networks, including context-specific gene regulatory networks and multi-omics partial correlation networks, to conduct differential analyses, estimate community structure, and model the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages (R, Python, MATLAB, and C) and between methods to allow a better integration of these tools into analytical pipelines. To demonstrate the value of this integrated toolkit, we analyzed the multi-omic data from the Cancer Cell Line Encyclopedia (CCLE) by inferring gene regulatory networks for each cancer cell line and associating network features with other phenotypic attributes such as drug sensitivity. This allowed us to identify transcription factors that play a critical role in both drug resistance and cancer development in melanoma. We also used netZoo to build a pan-cancer, multi-tiered CCLE map and used it to identify known metabolic hallmarks of cancer and to estimate novel context-specific elements that mediate post-transcriptional regulation. Because the netZoo tools are open-source and there is a growing community of both users and developers, we built an ecosystem to support community contributions, share use cases, and visualize networks online. As additional data types become available and our suite of methods grows, we will expand "the zoo" to incorporate an increasingly sophisticated collection of tools for network inference and analysis.

genomics↗