Dataset Information

Blind deconvolution estimation by multi-exponential models and alternated least squares approximations: Free-form and sparse approach.

ABSTRACT: The deconvolution process is a key step for quantitative evaluation of fluorescence lifetime imaging microscopy (FLIM) samples. By this process, the fluorescence impulse responses (FluoIRs) of the sample are decoupled from the instrument response (InstR). In blind deconvolution estimation (BDE), the FluoIRs and InstR are jointly extracted from a dataset with minimal a priori information. In this work, two BDE algorithms are introduced based on linear combinations of multi-exponential functions to model each FluoIR in the sample. For both schemes, the InstR is assumed with a free-form and a sparse structure. The local perspective of the BDE methodology assumes that the characteristic parameters of the exponential functions (time constants and scaling coefficients) are estimated based on a single spatial point of the dataset. On the other hand, the same exponential functions are used in the whole dataset in the global perspective, and just the scaling coefficients are updated for each spatial point. A least squares formulation is considered for both BDE algorithms. To overcome the nonlinear interaction in the decision variables, an alternating least squares (ALS) methodology iteratively solves both estimation problems based on non-negative and constrained optimizations. The validation stage considered first synthetic datasets at different noise types and levels, and a comparison with the standard deconvolution techniques with a multi-exponential model for FLIM measurements, as well as, with two BDE methodologies in the state of the art: Laguerre basis, and exponentials library. For the experimental evaluation, fluorescent dyes and oral tissue samples were considered. Our results show that local and global perspectives are consistent with the standard deconvolution techniques, and they reached the fastest convergence responses among the BDE algorithms with the best compromise in FluoIRs and InstR estimation errors.

SUBMITTER: Campos-Delgado DU

PROVIDER: S-EPMC7971520 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Tuning curves are the functions that relate the responses of sensory neurons to various values within one continuous stimulus dimension (such as the orientation of a bar in the visual domain or the frequency of a tone in the auditory domain). They are commonly determined by fitting a model e.g. a Gaussian or other bell-shaped curves to the measured responses to a small subset of discrete stimuli in the relevant dimension. However, as neuronal responses are irregular and experimental measurements noisy, it is often difficult to determine reliably the appropriate model from the data. We illustrate this general problem by fitting diverse models to representative recordings from area MT in rhesus monkey visual cortex during multiple attentional tasks involving complex composite stimuli. We find that all models can be well-fitted, that the best model generally varies between neurons and that statistical comparisons between neuronal responses across different experimental conditions are affected quantitatively and qualitatively by specific model choices. As a robust alternative to an often arbitrary model selection, we introduce a model-free approach, in which features of interest are extracted directly from the measured response data without the need of fitting any model. In our attentional datasets, we demonstrate that data-driven methods provide descriptions of tuning curve features such as preferred stimulus direction or attentional gain modulations which are in agreement with fit-based approaches when a good fit exists. Furthermore, these methods naturally extend to the frequent cases of uncertain model selection. We show that model-free approaches can identify attentional modulation patterns, such as general alterations of the irregular shape of tuning curves, which cannot be captured by fitting stereotyped conventional models. Finally, by comparing datasets across different conditions, we demonstrate effects of attention that are cell- and even stimulus-specific. Based on these proofs-of-concept, we conclude that our data-driven methods can reliably extract relevant tuning information from neuronal recordings, including cells whose seemingly haphazard response curves defy conventional fitting approaches.

Project description:BACKGROUND:Recent technological developments have enabled the measurement of a plethora of biomolecular data from various omics domains, and research is ongoing on statistical methods to leverage these omics data to better model and understand biological pathways and genetic architectures of complex phenotypes. Current reviews report that the simultaneous analysis of multiple (i.e. three or more) high dimensional omics data sources is still challenging and suitable statistical methods are unavailable. Often mentioned challenges are the lack of accounting for the hierarchical structure between omics domains and the difficulty of interpretation of genomewide results. This study is motivated to address these challenges. We propose multiset sparse Partial Least Squares path modeling (msPLS), a generalized penalized form of Partial Least Squares path modeling, for the simultaneous modeling of biological pathways across multiple omics domains. msPLS simultaneously models the effect of multiple molecular markers, from multiple omics domains, on the variation of multiple phenotypic variables, while accounting for the relationships between data sources, and provides sparse results. The sparsity in the model helps to provide interpretable results from analyses of hundreds of thousands of biomolecular variables. RESULTS:With simulation studies, we quantified the ability of msPLS to discover associated variables among high dimensional data sources. Furthermore, we analysed high dimensional omics datasets to explore biological pathways associated with Marfan syndrome and with Chronic Lymphocytic Leukaemia. Additionally, we compared the results of msPLS to the results of Multi-Omics Factor Analysis (MOFA), which is an alternative method to analyse this type of data. CONCLUSIONS:msPLS is an multiset multivariate method for the integrative analysis of multiple high dimensional omics data sources. It accounts for the relationship between multiple high dimensional data sources while it provides interpretable results through its sparse solutions. The biomarkers found by msPLS in the omics datasets can be interpreted in terms of biological pathways associated with the pathophysiology of Marfan syndrome and of Chronic Lymphocytic Leukaemia. Additionally, msPLS outperforms MOFA in terms of variation explained in the chronic lymphocytic leukaemia dataset while it identifies the two most important clinical markers for Chronic Lymphocytic Leukaemia AVAILABILITY: http://uva.csala.me/mspls.https://github.com/acsala/2018_msPLS.

Dataset Information

Blind deconvolution estimation by multi-exponential models and alternated least squares approximations: Free-form and sparse approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets