Biophysical reportsPub Date : 2024-09-11Epub Date: 2024-07-16DOI: 10.1016/j.bpr.2024.100172
Ivan V Prikhodko, Georgy Th Guria
{"title":"The method for assessing the specificity of developing CAR therapies.","authors":"Ivan V Prikhodko, Georgy Th Guria","doi":"10.1016/j.bpr.2024.100172","DOIUrl":"10.1016/j.bpr.2024.100172","url":null,"abstract":"<p><p>The effectiveness of antitumor chimeric antigen receptor (CAR) therapy mainly dealt with an elevated sensitivity of CAR cells to target cells. However, CAR therapies are associated with nonspecific side effects: on-target off-tumor toxicity. Sensitivity and specificity of CAR cells are the most important properties of the recognition process of target cells among other cells. Current developments are mainly concentrated on exploring molecular biology methods for designing CAR cells with the highest sensitivity, while the problem of the CAR cell specificity is rarely considered. For the assessment of CAR cell specificity, we suggest that, in addition to an elevated level of CAR-antigen affinity, the ability of CARs for clustering should be taken into account. We assume that the CAR cell cytotoxicity is determined by CAR clustering. The latter is treated within the framework of nucleation theory. The master equation for the probability of CAR cell cytotoxicity is derived. The size of a critical CAR cluster is found to be one of two most essential parameters. The conditions for necessary sensitivity and sufficient specificity are explored. Relevant parametric diagrams are derived. Possible applications of the method for assessing the specificity of developing CAR therapies are discussed.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":" ","pages":"100172"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2024-09-11Epub Date: 2024-06-05DOI: 10.1016/j.bpr.2024.100158
Adrian Ratwatte, Samitha Somathilaka, Sasitharan Balasubramaniam, Assaf A Gilad
{"title":"Nonlinear classifiers for wet-neuromorphic computing using gene regulatory neural network.","authors":"Adrian Ratwatte, Samitha Somathilaka, Sasitharan Balasubramaniam, Assaf A Gilad","doi":"10.1016/j.bpr.2024.100158","DOIUrl":"10.1016/j.bpr.2024.100158","url":null,"abstract":"<p><p>The gene regulatory network (GRN) of biological cells governs a number of key functionalities that enable them to adapt and survive through different environmental conditions. Close observation of the GRN shows that the structure and operational principles resemble an artificial neural network (ANN), which can pave the way for the development of wet-neuromorphic computing systems. Genes are integrated into gene-perceptrons with transcription factors (TFs) as input, where the TF concentration relative to half-maximal RNA concentration and gene product copy number influences transcription and translation via weighted multiplication before undergoing a nonlinear activation function. This process yields protein concentration as the output, effectively turning the entire GRN into a gene regulatory neural network (GRNN). In this paper, we establish nonlinear classifiers for molecular machine learning using the inherent sigmoidal nonlinear behavior of gene expression. The eigenvalue-based stability analysis, tailored to system parameters, confirms maximum-stable concentration levels, minimizing concentration fluctuations and computational errors. Given the significance of the stabilization phase in GRNN computing and the dynamic nature of the GRN, alongside potential changes in system parameters, we utilize the Lyapunov stability theorem for temporal stability analysis. Based on this GRN-to-GRNN mapping and stability analysis, three classifiers are developed utilizing two generic multilayer sub-GRNNs and a sub-GRNN extracted from the Escherichia coli GRN. Our findings also reveal the adaptability of different sub-GRNNs to suit different application requirements.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":" ","pages":"100158"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2024-09-11Epub Date: 2024-06-21DOI: 10.1016/j.bpr.2024.100166
Tim Altendorf, Jeannine Mohrlüder, Dieter Willbold
{"title":"TSAT: Efficient evaluation software for NGS data of phage/mirror-image phage display selections.","authors":"Tim Altendorf, Jeannine Mohrlüder, Dieter Willbold","doi":"10.1016/j.bpr.2024.100166","DOIUrl":"10.1016/j.bpr.2024.100166","url":null,"abstract":"<p><p>Phage display and mirror-image phage display are commonly used techniques for the identification of binders that are specific to predefined targets. Recent studies demonstrated the effectiveness of next-generation sequencing (NGS) by increasing the amount of information extracted from selections. This allows for a better analysis and increases the possibility to select effective binders. A potential downside to NGS analysis of phage display selections is the increased workload that is needed to analyze the obtained information. Here, we report on the development of TSAT (target-specific analysis tool), software for user-friendly and efficient analysis of peptide sequence data from NGS of phage display selections.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":" ","pages":"100166"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2024-09-11Epub Date: 2024-07-02DOI: 10.1016/j.bpr.2024.100170
Rupamanjari Majumder
{"title":"In silico thermal control of spiral wave dynamics in excitable cardiac tissue.","authors":"Rupamanjari Majumder","doi":"10.1016/j.bpr.2024.100170","DOIUrl":"10.1016/j.bpr.2024.100170","url":null,"abstract":"<p><p>Self-organizing spiral waves of excitation occur in many complex excitable systems. In the heart, for example, they are associated with the occurrence of fatal cardiac arrhythmias such as tachycardia and fibrillation, which can lead to sudden cardiac death. The control of these waves is therefore necessary for the treatment of the disease. In this letter, I present an innovative approach to control cardiac arrhythmias using low (nonfreezing) temperatures. This approach differs from all previous established techniques in that it involves no drugs, no genetic modification, no injection of foreign bodies, no application of voltage shocks (high or low, single or pulsed), and no curative damage to the heart. It relies on regional cooling of cardiac tissue to create a transient inhomogeneity in the electrophysiological properties. This inhomogeneity can then be manipulated to control the dynamics of the reentrant waves. This approach is, to my knowledge, the most sustainable theoretical proposal for the treatment of cardiac arrhythmias in the clinic.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":" ","pages":"100170"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2024-09-11Epub Date: 2024-06-22DOI: 10.1016/j.bpr.2024.100167
A M Whited, Irwin Jungreis, Jeffre Allen, Christina L Cleveland, Jonathan M Mudge, Manolis Kellis, John L Rinn, Loren E Hough
{"title":"Biophysical characterization of high-confidence, small human proteins.","authors":"A M Whited, Irwin Jungreis, Jeffre Allen, Christina L Cleveland, Jonathan M Mudge, Manolis Kellis, John L Rinn, Loren E Hough","doi":"10.1016/j.bpr.2024.100167","DOIUrl":"10.1016/j.bpr.2024.100167","url":null,"abstract":"<p><p>Significant efforts have been made to characterize the biophysical properties of proteins. Small proteins have received less attention because their annotation has historically been less reliable. However, recent improvements in sequencing, proteomics, and bioinformatics techniques have led to the high-confidence annotation of small open reading frames (smORFs) that encode for functional proteins, producing smORF-encoded proteins (SEPs). SEPs have been found to perform critical functions in several species, including humans. While significant efforts have been made to annotate SEPs, less attention has been given to the biophysical properties of these proteins. We characterized the distributions of predicted and curated biophysical properties, including sequence composition, structure, localization, function, and disease association of a conservative list of previously identified human SEPs. We found significant differences between SEPs and both larger proteins and control sets. In addition, we provide an example of how our characterization of biophysical properties can contribute to distinguishing protein-coding smORFs from noncoding ones in otherwise ambiguous cases.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":" ","pages":"100167"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2024-06-12Epub Date: 2024-04-24DOI: 10.1016/j.bpr.2024.100156
Conrad Möckel, Timon Beck, Sara Kaliman, Shada Abuhattum, Kyoohyun Kim, Julia Kolb, Daniel Wehner, Vasily Zaburdaev, Jochen Guck
{"title":"Estimation of the mass density of biological matter from refractive index measurements.","authors":"Conrad Möckel, Timon Beck, Sara Kaliman, Shada Abuhattum, Kyoohyun Kim, Julia Kolb, Daniel Wehner, Vasily Zaburdaev, Jochen Guck","doi":"10.1016/j.bpr.2024.100156","DOIUrl":"10.1016/j.bpr.2024.100156","url":null,"abstract":"<p><p>The quantification of physical properties of biological matter gives rise to novel ways of understanding functional mechanisms. One of the basic biophysical properties is the mass density (MD). It affects the dynamics in sub-cellular compartments and plays a major role in defining the opto-acoustical properties of cells and tissues. As such, the MD can be connected to the refractive index (RI) via the well known Lorentz-Lorenz relation, which takes into account the polarizability of matter. However, computing the MD based on RI measurements poses a challenge, as it requires detailed knowledge of the biochemical composition of the sample. Here we propose a methodology on how to account for assumptions about the biochemical composition of the sample and respective RI measurements. To this aim, we employ the Biot mixing rule of RIs alongside the assumption of volume additivity to find an approximate relation of MD and RI. We use Monte-Carlo simulations and Gaussian propagation of uncertainty to obtain approximate analytical solutions for the respective uncertainties of MD and RI. We validate this approach by applying it to a set of well-characterized complex mixtures given by bovine milk and intralipid emulsion and employ it to estimate the MD of living zebrafish (Danio rerio) larvae trunk tissue. Our results illustrate the importance of implementing this methodology not only for MD estimations but for many other related biophysical problems, such as mechanical measurements using Brillouin microscopy and transient optical coherence elastography.</p>","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":"4 2","pages":"100156"},"PeriodicalIF":2.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biophysical reportsPub Date : 2023-12-03eCollection Date: 2023-12-13DOI: 10.1016/j.bpr.2023.100136
{"title":"Thank you to our reviewers.","authors":"","doi":"10.1016/j.bpr.2023.100136","DOIUrl":"https://doi.org/10.1016/j.bpr.2023.100136","url":null,"abstract":"","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":"3 4","pages":"100136"},"PeriodicalIF":0.0,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10746389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phasor Identifier: A Cloud-based Analysis of Phasor-FLIM Data on Python Notebooks","authors":"Mario Bernardi, Francesco Cardarelli","doi":"10.1016/j.bpr.2023.100135","DOIUrl":"https://doi.org/10.1016/j.bpr.2023.100135","url":null,"abstract":"This paper introduces an innovative approach utilizing Google Colaboratory (Colab) for the versatile analysis of phasor Fluorescence Lifetime Imaging Microscopy (FLIM) data collected from various samples (e.g., cuvette, cells, tissues) and in various input file formats. In fact, phasor-FLIM widespread adoption has been hampered by complex instrumentation and data analysis requirements. We mean to make advanced FLIM analysis more accessible to researchers through a cloud-based solution that i) harnesses robust computational resources, ii) eliminates hardware limitations, iii) supports both CPU and GPU processing, We envision a paradigm shift in FLIM data accessibility and potential, aligning with the evolving field of AI-driven FLIM analysis. This approach simplifies FLIM data handling and opens doors for diverse applications, from studying cellular metabolism to investigating drug encapsulation, benefiting researchers across multiple domains. The comparative analysis of freely distributed FLIM tools highlights the unique advantages of this approach in terms of adaptability, scalability, and open-source nature.","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":"133 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135509635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Imboden, Xuanqing Liu, Marie C. Payne, Cho-Jui Hsieh, Neil Y.C. Lin
{"title":"Trustworthy in silico Cell Labeling via Ensemble-based Image Translation","authors":"Sara Imboden, Xuanqing Liu, Marie C. Payne, Cho-Jui Hsieh, Neil Y.C. Lin","doi":"10.1016/j.bpr.2023.100133","DOIUrl":"https://doi.org/10.1016/j.bpr.2023.100133","url":null,"abstract":"Artificial Intelligence (AI) image translation has been a valuable tool for processing image data in biological and medical research. To apply such a tool in mission-critical applications including drug screening, toxicity study, and clinical diagnostics, it is essential to ensure that the AI prediction is trustworthy. Here, we demonstrated that an ensemble learning method can quantify the uncertainty of AI image translation. We tested the uncertainty evaluation using experimentally acquired images of mesenchymal stromal cells (MSCs). We found that the ensemble method reports a prediction standard deviation that correlates with the prediction error, estimating the prediction uncertainty. We showed that this uncertainty is in agreement with the prediction error and Pearson correlation coefficient. We further showed that the ensemble method can detect out-of-distribution input images by reporting increased uncertainty. Altogether, these results suggest that the ensemble-estimated uncertainty can be a useful indicator for identifying erroneous AI image translations.","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135850388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thioflavin T indicates membrane potential in mammalian cells and can affect it in a blue light dependent manner.","authors":"Emily Skates, Hadrien Delattre, Zoe Schofield, Munehiro Asally, Orkun S. Soyer","doi":"10.1016/j.bpr.2023.100134","DOIUrl":"https://doi.org/10.1016/j.bpr.2023.100134","url":null,"abstract":"The fluorescent benzothiazole dye Thioflavin T (ThT) is widely used as a marker for protein aggregates, most commonly in the context of neurodegenerative disease research and diagnosis. Recently, this same dye was shown to indicate membrane potential in bacteria due to its cationic nature. This finding prompted a question whether ThT fluorescence is linked to the membrane potential in mammalian cells, which would be important for appropriate utilisation of ThT in research and diagnosis. Here, we show that ThT localises into the mitochondria of HeLa cells in a membrane-potential dependent manner. Specifically, ThT colocalised in cells with the mitochondrial membrane-potential indicator Tetramethylrhodamine methyl ester (TMRM) and gave similar temporal responses as TMRM to treatment with a protonophore, carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP). Additionally, we found that presence of ThT together with exposure to blue light (λ = 405 nm), but neither factor alone, caused depolarisation of mitochondrial membrane potential. This additive effect of the concentration and blue light was recapitulated by a mathematical model implementing the potential-dependent distribution of ThT and its effect on mitochondrial membrane potential through photosensitization. These results show that ThT can act as a mitochondrial membrane potential indicator in mammalian cells, when used at low concentrations and with low blue-light exposure. However, it causes dissipation of the mitochondrial membrane potential depending additively on its concentrations and blue light exposure. This conclusion motivates a re-evaluation of ThT’s use at micromolar range in live-cell analyses, and indicates that this dye can enable future studies on the potential connections between membrane potential dynamics and protein aggregation.","PeriodicalId":72402,"journal":{"name":"Biophysical reports","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136128399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}