Biology subjects

Auth, J. M.

Publications and source records attributed to Auth, J. M..

3 recordsLinked to original sources

bioRxiv2026

Integration of proteomic data from cell lines and tumors

Cancer cell lines are widely used in preclinical research, yet the clinical translation of findings from cell lines remains limited. Identifying cell lines that best resemble patient tumors requires integration of molecular profiles across biologically distinct sample types. Advances in transcriptomic integration have demonstrated the potential of deep learning for aligning data across different sample types. However, comparable approaches for proteomic data integration remain lacking, potentially because of the prevalence of missing values in proteomic datasets. Here, we introduce ProtInt, a deep learning-based framework that integrates proteomic data by combining principles from proteomic imputation and transcriptomic integration methods. We applied ProtInt to integrate label-free proteomic profiles from 771 cancer cell lines and 550 treatment-naive tumors, and showed that ProtInt outperformed batch correction and transcriptomic integration methods. Comparison of the cell line proteomes before and after integration revealed recurrent increase of proteins associated with immune reaction and reduction of proteins involved in mitochondrial gene expression as proteomes of cell lines were adapted to resemble tumors. These results establish ProtInt as a framework for joint analysis of proteomic datasets across distinct sample types and may facilitate the identification of cell lines best suited for clinically relevant studies.

bioinformatics↗

bioRxiv2026

Asymmetric crosstalk between the BMP and TGFβ pathways resolves signaling ambiguity

The BMP and TGF{beta} signaling pathways control cellular fate decisions in diverse biological contexts, often playing opposing roles. Despite extensive knowledge of these pathways, understanding how cells respond to environments containing these opposing cues remains a challenge. Here, we systematically analyze the activation of these pathways under combinatorial signaling environments. We find that TGF{beta} ligands inhibit BMP signaling, while BMP ligands enhance TGF{beta} transcriptional response across concentrations, ligand variants, and cell types. This asymmetric crosstalk results in the activation of a TGF{beta}-biased transcriptional response, even under mixed signaling conditions, effectively reducing signal ambiguity, with implications for processes such as EMT. We show that this crosstalk originates downstream of the SMAD proteins phosphorylation. Using mathematical models, we predict, and experimentally verify, that promiscuous interactions between SMAD proteins provide the mechanism for the observed crosstalk. Our findings challenge the canonical models, suggesting an active role for mediator proteins in determining biological responses.

systems biology↗

bioRxiv2018

The interplay of synaptic plasticity and scaling enables the self-organized allocation of multiple memory representations

It is commonly assumed that memories about experienced stimuli are represented by groups of highly interconnected neurons called cell assemblies. This requires allocating and storing information in the neural circuitry, which happens through synaptic weight adaptation. It remains, however, largely unknown how memory allocation and storage can be achieved and coordinated to allow for a faithful representation of multiple memories without disruptive interference between them. In this theoretical study, we show that the interplay between conventional synaptic plasticity and homeostatic synaptic scaling organizes synaptic weight adaptations such that a new stimulus forms a new memory and where different stimuli are assigned to distinct cell assemblies. The resulting dynamics can reproduce experimental in-vivo data, focusing on how diverse factors as neuronal excitability and network connectivity, influence memory formation. Thus, the here presented model suggests that a few fundamental synaptic mechanisms may suffice to implement memory allocation and storage in neural circuitry.

neuroscience↗