In biology, cell motility is a valuable indicator, revealing how cells sense their environment, adapt to stimuli, and reflect their physiological state. In this paper, we present a modular microscopy system designed to study the motility of microorganisms. The setup is compact, assembled from low-cost 3D-printed and widely available components. It integrates programmable multispectral illumination to enable controlled photo stimulation and investigation of light-induced behavioral responses, including phototaxis. Initially developed for the investigation of photosynthetic microalgae, the system is easily adaptable to a wide range of motile microorganisms. It supports two complementary observation modes: a droplet-based chamber that minimizes sedimentation for cell speed analysis, and a deeper chamber that allows sedimentation, enabling quantitative assessment of motility fraction and orientation relative to directional light. The optical system provides a magnification of up to approximately 9×, sufficient for the precise centroid detection and tracking of single cells. This open-source, DIY (Do It Yourself) microscopy platform offers an accessible tool for photobiology, microbial ecology, and biophysics, helping democratize quantitative motility studies

The question whether Covid-19 vaccination campaigns could have had an immediate negative impact on excess deaths continues to be debated two years later, in particular in the less than 45 years old. When the age-stratified (anonymized) vaccination status of deceased will be publicly available, the debate should come to an end. In the meantime, this paper provides three new statistical analyses that further shed light on the matter. Two of them connect the temporality of all-cause mortality data with injection data. Another analysis, using internet search trends, investigates possible alternative explanations. We deem that taken together, as it is done in this paper, those three analyses reinforce our previous conclusions suggesting caution when it comes to vaccinating/boosting young European populations.

Sarcoidosis and lymphoma often share common features on 18F-FDG PET/CT, such as intense hypermetabolic lesions in lymph nodes and multiple organs. We aimed at developing and validating radiomics signatures to differentiate sarcoidosis from Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively collected 420 patients (169 sarcoidosis, 140 HL, and 111 DLBCL) who underwent pretreatment 18F-FDG PET/CT at the University Hospital of Liege. The studies were randomly distributed to 4 physicians, who gave their diagnostic suggestion among the 3 diseases. The individual and pooled performance of the physicians was then calculated. Interobserver variability was evaluated using a sample of 34 studies interpreted by all physicians. Volumes of interest were delineated over the lesions and the liver using MIM software, and 215 radiomics features were extracted using the RadiomiX Toolbox. Models were developed combining clinical data (age, sex, and weight) and radiomics (original and tumor-to-liver TLR radiomics), with 7 different feature selection approaches and 4 different machine-learning (ML) classifiers, to differentiate sarcoidosis and lymphomas on both lesion-based and patient-based approaches. Results: For identifying lymphoma versus sarcoidosis, physicians' pooled sensitivity, specificity, area under the receiver-operating-characteristic curve (AUC), and accuracy were 0.99 (95% CI, 0.97-1.00), 0.75 (95% CI, 0.68-0.81), 0.87 (95% CI, 0.84-0.90), and 89.3%, respectively, whereas for identifying HL in the tumor population, it was 0.58 (95% CI, 0.49-0.66), 0.82 (95% CI, 0.74-0.89), 0.70 (95% CI, 0.64-0.75) and 68.5%, respectively. Moderate agreement was found among observers for the diagnosis of lymphoma versus sarcoidosis and HL versus DLBCL, with Fleiss κ-values of 0.66 (95% CI, 0.45-0.87) and 0.69 (95% CI, 0.45-0.93), respectively. The best ML models for identifying lymphoma versus sarcoidosis showed an AUC of 0.94 (95% CI, 0.93-0.95) and 0.85 (95% CI, 0.82-0.88) in lesion- and patient-based approaches, respectively, using TLR radiomics (plus age for the second). To differentiate HL from DLBCL, we obtained an AUC of 0.95 (95% CI, 0.93-0.96) in the lesion-based approach using TLR radiomics and 0.86 (95% CI, 0.80-0.91) in the patient-based approach using original radiomics and age. Conclusion: Characterization of sarcoidosis and lymphoma lesions is feasible using ML and radiomics, with very good to excellent performance, equivalent to or better than that of physicians, who showed significant interobserver variability in their assessment.

Bright field microscopes are particularly useful tools for biologists for cell and tissue observation, phenotyping, cell counting, and so on. Direct cell observation provides a wealth of information on cells’ nature and physiological condition. Microscopic analyses are, however, time-consuming and usually not easy to parallelize. We describe the fabrication of a stand-alone microscope able to automatically collect samples with 3D printed pumps, and capture images at up to 50× optical magnification with a digital camera at a good throughput (up to 24 different samples can be collected and scanned in less than 10 min). Furthermore, the proposed device can store and analyze pictures using computer vision algorithms running on a low power integrated single board computer. Our device can perform a large set of tasks, with minimal human intervention, that no single commercially available machine can perform. The proposed open-hardware device has a modular design and can be freely reproduced at a very competitive price with the use of widely documented and user-friendly components such as Arduino, Raspberry pi, and 3D printers.

Background Features reproducibility and the generalizability of the models are currently among the most important limitations when integrating radiomics into the clinics. Radiomic features are sensitive to imaging acquisition protocols, reconstruction algorithms and parameters, as well as by the different steps of the usual radiomics workflow. We propose a framework for comparing the reproducibility of different pre-processing steps in PET/CT radiomic analysis in the prediction of disease free survival (DFS) across multi-scanners/centers. Results We evaluated and compared the prediction performance of several models that differ in i) the type of intensity discretization, ii) feature selection method, iii) features type i.e, original or tumour to liver ratio radiomic features (OR or TLR). We trained our models using data from one scanner/center and tested on two external scanner/centers. Our results show that there is a low reproducibility in predictions across scanners and discretization methods. Despite of this, TLR based models were generally more robust than OR. Maximum relevance minimum redundancy (MRMR) forward feature selection with Pearson correlation was the feature selection method that had the best mean area under the precision recall curve when using it combining the features from all discretization’s bin’s number (D_All_FBN) with TLR features for two of the four classifiers. Conclusion We evaluated and compared the prediction performance of several models in a data set containing hundred fifty-eight patients with locally advanced cervical cancer (LACC) from three distinct scanners. In our cohort of LAAC patients pre-processing of radiomic features in [ 18 F]FDG PET affects DFS predictions performances across scanners and combining the D_All_FBN TLR approach with the MRMR forward Pearson feature selection method might help increasing robustness of radiomic studies.

A correction to this paper has been published: https://doi.org10.1007/s00259-021-05397-x

Many routines in biological experiments require the precise handling of liquid volumes in the range of microliters up to liters. In this paper, we describe a new wireless controller that is adapted to liquid manipulation tasks, in particular when combined with the proposed 3D-printed pumps. It can be built from widely available electronic components and managed with open-source software. The use of peristaltic pumps enables to move volumes from milliliters to liters with a relative error below 1% or a syringe pump capable of injecting volumes in the range of milliliters with microliter accuracy. The system is remotely controllable over WiFi and easily automated using the MQTT communication protocol. The programming of the microcontroller is performed on the Arduino IDE. The WiFi settings and the calibration value can be easily modified, stored and exported in the form of a JSON file to create a user friendly, plug and play and easily scalable device. Additional sensors or actuators can be added, allowing the system to adapt to various usages. Finally, in addition to its low manufacturing cost and its capability to fit a large variety of tasks involving liquid handling, our system has been specifically designed for research environments where adaptability and repeatability of experiments is essential.

Keeping an algal culture at a constant turbidity requires expensive and complex devices. We designed a low-cost, user friendly but also highly configurable phototurbidostat using 3D-printing, open-source software and electronics. The device is able to monitor in real time a culture in photobioreactor, and dynamically adjust the conditions to maintain the turbidity at a desired value. It can accommodate to a large set of volumes or laboratory equipments with little effort thanks to its modular and scalable design. Each module (such as light, pumps or sensors) are autonomous and controllable via Wi-Fi. Furthermore, our phototurbidostat is fully open-source and can be remotely controlled by a smartphone or a computer via a web-based graphical user interface. Finally, the device can be reproduced easily for a cost ranging between 1/20th and 1/50th of the price of a classical commercial device.

Inferring gene regulatory networks from expression data is a very challenging problem that has raised the interest of the scientific community. Different algorithms have been proposed to try to solve this issue, but it has been shown that different methods have some particular biases and strengths, and none of them is the best across all types of data and datasets. As a result, the idea of aggregating various network inferences through a consensus mechanism naturally arises. In this chapter, a common framework to standardize already proposed consensus methods is presented, and based on this framework different proposals are introduced and analyzed in two different scenarios: Homogeneous and Heterogeneous. The first scenario reflects situations where the networks to be aggregated are rather similar because they are obtained with inference algorithms working on the same data, whereas the second scenario deals with very diverse networks because various sources of data are used to generate the individual networks. A procedure for combining multiple network inference algorithms is analyzed in a systematic way. The results show that there is a very significant difference between these two scenarios, and that the best way to combine networks in the Heterogeneous scenario is not the most commonly used. We show in particular that aggregation in the Heterogeneous scenario can be very beneficial if the individual networks are combined with our new proposed method ScaleLSum.

Genetic analyses of plant root systems require large datasets of extracted architectural traits. To quantify such traits from images of root systems, researchers often have to choose between automated tools (that are prone to error and extract only a limited number of architectural traits) or semi-automated ones (that are highly time consuming). We trained a Random Forest algorithm to infer architectural traits from automatically extracted image descriptors. The training was performed on a subset of the dataset, then applied to its entirety. This strategy allowed us to (i) decrease the image analysis time by 73% and (ii) extract meaningful architectural traits based on image descriptors. We also show that these traits are sufficient to identify the quantitative trait loci that had previously been discovered using a semi-automated method. We have shown that combining semi-automated image analysis with machine learning algorithms has the power to increase the throughput of large-scale root studies. We expect that such an approach will enable the quantification of more complex root systems for genetic studies. We also believe that our approach could be extended to other areas of plant phenotyping.

Root system analysis is a complex task, often performed with fully automated image analysis pipelines. However, the outcome is rarely verified by ground-truth data, which might lead to underestimated biases. We have used a root model, ArchiSimple, to create a large and diverse library of ground-truth root system images (10,000). For each image, three levels of noise were created. This library was used to evaluate the accuracy and usefulness of several image descriptors classically used in root image analysis softwares. Our analysis highlighted that the accuracy of the different traits is strongly dependent on the quality of the images and the type, size, and complexity of the root systems analyzed. Our study also demonstrated that machine learning algorithms can be trained on a synthetic library to improve the estimation of several root system traits. Overall, our analysis is a call to caution when using automatic root image analysis tools. If a thorough calibration is not performed on the dataset of interest, unexpected errors might arise, especially for large and complex root images. To facilitate such calibration, both the image library and the different codes used in the study have been made available to the community.

Background Reverse engineering of gene regulatory networks (GRNs) from gene expression data is a classical challenge in systems biology. Thanks to high-throughput technologies, a massive amount of gene-expression data has been accumulated in the public repositories. Modelling GRNs from multiple experiments (also called integrative analysis) has; therefore, naturally become a standard procedure in modern computational biology. Indeed, such analysis is usually more robust than the traditional approaches, which suffer from experimental biases and the low number of samples by analysing individual datasets. To date, there are mainly two strategies for the problem of interest: the first one (“data merging”) merges all datasets together and then infers a GRN whereas the other (“networks ensemble”) infers GRNs from every dataset separately and then aggregates them using some ensemble rules (such as ranksum or weightsum). Unfortunately, a thorough comparison of these two approaches is lacking. Results In this work, we are going to present another meta-analysis approach for inferring GRNs from multiple studies. Our proposed meta-analysis approach, adapted to methods based on pairwise measures such as correlation or mutual information, consists of two steps: aggregating matrices of the pairwise measures from every dataset followed by extracting the network from the meta-matrix. Afterwards, we evaluate the performance of the two commonly used approaches mentioned above and our presented approach with a systematic set of experiments based on in silico benchmarks. Conclusions We proposed a first systematic evaluation of different strategies for reverse engineering GRNs from multiple datasets. Experiment results strongly suggest that assembling matrices of pairwise dependencies is a better strategy for network inference than the two commonly used ones.

Biomedical scientific literature is an unexploited treasure. Due to the staggering number of publications it is literally intractable to gather manually all information. Automatized information extraction (IE) is therefore key. An important subtask is the recognition of names in the text as specific entities (named entity recognition, NER). NER for genes in biomedical literature is a challenging task. This paper reports preliminary results for the identification of gene names in full text with the naive Bayes, support vector machine and random forest algorithms, showing that there is no loss on performance compared to the gene NER restricted to abstracts.

Background Genetic analyses of plant root system development require large datasets of extracted architectural traits. To quantify such traits from images of root systems, researchers often have to choose between automated tools (that are prone to error and extract only a limited number of architectural traits) or semi-automated ones (that are highly time consuming). Findings We trained a Random Forest algorithm to infer architectural traits from automatically-extracted image descriptors. The training was performed on a subset of the dataset, then applied to its entirety. This strategy allowed us to (i) decrease the image analysis time by 73% and (ii) extract meaningful architectural traits based on image descriptors. We also show that these traits are sufficient to identify Quantitative Trait Loci that had previously been discovered using a semi-automated method. Conclusions We have shown that combining semi-automated image analysis with machine learning algorithms has the power to increase the throughput in large scale root studies. We expect that such an approach will enable the quantification of more complex root systems for genetic studies. We also believe that our approach could be extended to other area of plant phenotyping.

This paper presents a novel method for the reconstruction of a neural network connectivity using calcium fluorescence data. We introduce a fast unsupervised method to integrate different networks that reconstructs structural connectivity from neuron activity. Our method improves the state-of-the-art reconstruction method General Transfer Entropy (GTE). We are able to better eliminate indirect links, improving therefore the quality of the network via a normalization and ensemble process of GTE and three new informative features. The approach is based on a simple combination of networks, which is remarkably fast. The performance of our approach is benchmarked on simulated time series provided at the connectomics challenge and also submitted at the public competition.

BACKGROUND:In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods.RESULTS:Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities.CONCLUSIONS:The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.