Motivation Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.e. data where the intervention was not applied randomly, for both continuous and binary outcome variables. However, patient outcome is often recorded in terms of time-to-event data, comprising right-censored event times if an event does not occur within the observation period. Albeit their enormous importance, time-to-event data are rarely used for treatment optimization. We suggest an approach named BITES (Balanced Individual Treatment Effect for Survival data), which combines a treatment-specific semi-parametric Cox loss with a treatment-balanced deep neural network; i.e. we regularize differences between treated and non-treated patients using Integral Probability Metrics (IPM). Results We show in simulation studies that this approach outperforms the state of the art. Furthermore, we demonstrate in an application to a cohort of breast cancer patients that hormone treatment can be optimized based on six routine parameters. We successfully validated this finding in an independent cohort. Availability and implementation We provide BITES as an easy-to-use python implementation including scheduled hyper-parameter optimization (https://github.com/sschrod/BITES). The data underlying this article are available in the CRAN repository at https://rdrr.io/cran/survival/man/gbsg.html and https://rdrr.io/cran/survival/man/rotterdam.html. Supplementary information Supplementary data are available at Bioinformatics online.
Motivation: The 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 prototypes 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 as such, pre-specified cell prototypes can distort the inference of cellular compositions. Results: We 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 the prototypic reference profiles to the molecular environment of the cells, which allows one to resolve cell-type specific regulation from bulk transcriptomics data. The performance of ADTD was verified in simulation studies, and in an application to breast cancer data we demonstrate how ADTD can be used to gain insights into molecular differences between breast cancer sub-types. Availability and implementation: A python implementation of ADTD and a tutorial are available at https://doi.org/10.5281/zenodo.7548362
Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.e. data where the intervention was not applied randomly, for both continuous and binary outcome variables. However, patient outcome is often recorded in terms of time-to-event data, comprising right-censored event times if an event does not occur within the observation period. Albeit their enormous importance, time-to-event data is rarely used for treatment optimization.We suggest an approach named BITES (Balanced Individual Treatment Effect for Survival data), which combines a treatment-specific semiparametric Cox loss with a treatment-balanced deep neural network; i.e. we regularize differences between treated and non-treated patients using Integral Probability Metrics (IPM). We show in simulation studies that this approach outperforms the state of the art. Further, we demonstrate in an application to a cohort of breast cancer patients that hormone treatment can be optimized based on six routine parameters. We successfully validated this finding in an independent cohort.
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 and transduced through signaling cascades from the membrane to the nucleus, 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 (capturing 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.
We demonstrate the use of white-light spectral interferometry as an effective technique involving only linear optical interactions and a partially coherent light source to measure the complex transmission response function of optical resonance and to determine the corresponding variation in the refractive index relative to a reference. We also discuss experimental arrangements to increase the accuracy and sensitivity of the technique. The superiority of the technique over single-beam absorption measurements is demonstrated by the accurate determination of the response function of the chlorophyll-a solution. The technique is then applied to chlorophyll-a solutions of varying concentrations and gold nanocolloids to characterize inhomogeneous broadening. Results on the inhomogeneity of gold nanocolloids are also supported by transmission electron micrographs, showing distributions of the size and shape of the constituent gold nanorods.
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