Gene regulatory network inference : connecting plant biology and mathematical modeling

Plant responses to environmental and intrinsic signals are tightly controlled by multiple transcription factors (TFs). These TFs and their regulatory connections form gene regulatory networks (GRNs), which provide a blueprint of the transcriptional regulations underlying plant development and environmental responses. This review provides examples of experimental methodologies commonly used to identify regulatory interactions and generate GRNs. Additionally, this review describes network inference techniques that leverage gene expression data to predict regulatory interactions. These computational and experimental methodologies yield complex networks that can identify new regulatory interactions, driving novel hypotheses. Biological properties that contribute to the complexity of GRNs are also described in this review. These include network topology, network size, transient binding of TFs to DNA, and competition between multiple upstream regulators. Finally, this review highlights the potential of machine learning approaches to leverage gene expression data to predict phenotypic outputs

Deployment and Analysis of Instance Segmentation Algorithm for In-field Grade Estimation of Sweetpotatoes

Shape estimation of sweetpotato (SP) storage roots is inherently challenging due to their varied size and shape characteristics. Even measuring "simple" metrics, such as length and width, requires significant time investments either directly in-field or afterward using automated graders. In this paper, we present the results of a model that can perform grading and provide yield estimates directly in the field quicker than manual measurements. Detectron2, a library consisting of deep-learning object detection algorithms, was used to implement Mask R-CNN, an instance segmentation model. This model was deployed for in-field grade estimation of SPs and evaluated against an optical sorter. Storage roots from various clones imaged with a cellphone during trials between 2019 and 2020, were used in the model's training and validation to fine-tune a model to detect SPs. Our results showed that the model could distinguish individual SPs in various environmental conditions including variations in lighting and soil characteristics. RMSE for length, width, and weight, from the model compared to a commercial optical sorter, were 0.66 cm, 1.22 cm, and 74.73 g, respectively, while the RMSE of root counts per plot was 5.27 roots, with r^2 = 0.8. This phenotyping strategy has the potential enable rapid yield estimates in the field without the need for sophisticated and costly optical sorters and may be more readily deployed in environments with limited access to these kinds of resources or facilities.Comment: 21 pages, 11 figure

A novel cost function to estimate parameters of oscillatory biochemical systems

Oscillatory pathways are among the most important classes of biochemical systems with examples ranging from circadian rhythms and cell cycle maintenance. Mathematical modeling of these highly interconnected biochemical networks is needed to meet numerous objectives such as investigating, predicting and controlling the dynamics of these systems. Identifying the kinetic rate parameters is essential for fully modeling these and other biological processes. These kinetic parameters, however, are not usually available from measurements and most of them have to be estimated by parameter fitting techniques. One of the issues with estimating kinetic parameters in oscillatory systems is the irregularities in the least square (LS) cost function surface used to estimate these parameters, which is caused by the periodicity of the measurements. These irregularities result in numerous local minima, which limit the performance of even some of the most robust global optimization algorithms. We proposed a parameter estimation framework to address these issues that integrates temporal information with periodic information embedded in the measurements used to estimate these parameters. This periodic information is used to build a proposed cost function with better surface properties leading to fewer local minima and better performance of global optimization algorithms. We verified for three oscillatory biochemical systems that our proposed cost function results in an increased ability to estimate accurate kinetic parameters as compared to the traditional LS cost function. We combine this cost function with an improved noise removal approach that leverages periodic characteristics embedded in the measurements to effectively reduce noise. The results provide strong evidence on the efficacy of this noise removal approach over the previous commonly used wavelet hard-thresholding noise removal methods. This proposed optimization framework results in more accurate kinetic parameters that will eventually lead to biochemical models that are more precise, predictable, and controllable

The next generation of training for arabidopsis researchers: Bioinformatics and Quantitative Biology

It has been more than 50 years since Arabidopsis (Arabidopsis thaliana) was first introduced as a model organism to understand basic processes in plant biology. A well-organized scientific community has used this small reference plant species to make numerous fundamental plant biology discoveries (Provart et al., 2016). Due to an extremely well-annotated genome and advances in high-throughput sequencing, our understanding of this organism and other plant species has become even more intricate and complex. Computational resources, including CyVerse,3 Araport,4 The Arabidopsis Information Resource (TAIR),5 and BAR,6 have further facilitated novel findings with just the click of a mouse. As we move toward understanding biological systems, Arabidopsis researchers will need to use more quantitative and computational approaches to extract novel biological findings from these data. Here, we discuss guidelines, skill sets, and core competencies that should be considered when developing curricula or training undergraduate or graduate students, postdoctoral researchers, and faculty. A selected case study provides more specificity as to the concrete issues plant biologists face and how best to address such challenges

Set membership experimental design for biological systems

BACKGROUND: Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. RESULTS: In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. CONCLUSIONS: The practicability of our approach is illustrated with a case study. This study shows that our approach is able to 1) identify candidate measurement time points that maximize information corresponding to biologically relevant metrics and 2) determine the number at which additional measurements begin to provide insignificant information. This framework can be used to balance the availability of resources with the addition of one or more measurement time points to improve the predictability of resulting models

Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the coronavirus disease 2019 (COVID-19) pandemic. Though previous studies have suggested that SARS-CoV-2 cellular tropism depends on the host-cell-expressed proteins, whether transcriptional regulation controls SARS-CoV-2 tropism factors in human lung cells remains unclear. In this study, we used computational approaches to identify transcription factors (TFs) regulating SARS-CoV-2 tropism for different types of lung cells. We constructed transcriptional regulatory networks (TRNs) controlling SARS-CoV-2 tropism factors for healthy donors and COVID-19 patients using lung single-cell RNA-sequencing (scRNA-seq) data. Through differential network analysis, we found that the altered regulatory role of TFs in the same cell types of healthy and SARS-CoV-2-infected networks may be partially responsible for differential tropism factor expression. In addition, we identified the TFs with high centralities from each cell type and proposed currently available drugs that target these TFs as potential candidates for the treatment of SARS-CoV-2 infection. Altogether, our work provides valuable cell-type-specific TRN models for understanding the transcriptional regulation and gene expression of SARS-CoV-2 tropism factors

Internal defect scanning of sweetpotatoes using interactance spectroscopy.

While standard visible-light imaging offers a fast and inexpensive means of quality analysis of horticultural products, it is generally limited to measuring superficial (surface) defects. Using light at longer (near-infrared) or shorter (X-ray) wavelengths enables the detection of superficial tissue bruising and density defects, respectively; however, it does not enable the optical absorption and scattering properties of sub-dermal tissue to be quantified. This paper applies visible and near-infrared interactance spectroscopy to detect internal necrosis in sweetpotatoes and develops a Zemax scattering simulation that models the measured optical signatures for both healthy and necrotic tissue. This study demonstrates that interactance spectroscopy can detect the unique near-infrared optical signatures of necrotic tissues in sweetpotatoes down to a depth of approximately 5±0.5 mm. We anticipate that light scattering measurement methods will represent a significant improvement over the current destructive analysis methods used to assay for internal defects in sweetpotatoes

Incorporating spatial information into entropy estimates to improve multimodal image registration

ABSTRACT We propose an approach to incorporate spatial information into the estimate of the entropy of an image by partitioning a high-dimensional space into regions over which a onedimensional histogram can be indexed. This approach obviates the need for the construction of high-dimensional histograms and makes no assumptions on the form of the high-dimensional probability mass function. We use this partitioned estimate of entropy to compute image similarity measures, useful in image registration, and we examine the convergence properties of the registration process

Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa.

Accurate manipulation of metabolites in monolignol biosynthesis is a key step for controlling lignin content, structure, and other wood properties important to the bioenergy and biomaterial industries. A crucial component of this strategy is predicting how single and combinatorial knockdowns of monolignol specific gene transcripts influence the abundance of monolignol proteins, which are the driving mechanisms of monolignol biosynthesis. Computational models have been developed to estimate protein abundances from transcript perturbations of monolignol specific genes. The accuracy of these models, however, is hindered by their inability to capture indirect regulatory influences on other pathway genes. Here, we examine the manifestation of these indirect influences on transgenic transcript and protein abundances, identifying putative indirect regulatory influences that occur when one or more specific monolignol pathway genes are perturbed. We created a computational model using sparse maximum likelihood to estimate the resulting monolignol transcript and protein abundances in transgenic Populus trichocarpa based on targeted knockdowns of specific monolignol genes. Using in-silico simulations of this model and root mean square error, we showed that our model more accurately estimated transcript and protein abundances, in comparison to previous models, when individual and families of monolignol genes were perturbed. We leveraged insight from the inferred network structure obtained from our model to identify potential genes, including PtrHCT, PtrCAD, and Ptr4CL, involved in post-transcriptional and/or post-translational regulation. Our model provides a useful computational tool for exploring the cascaded impact of single and combinatorial modifications of monolignol specific genes on lignin and other wood properties

The first order sensitivity index for monolignol flux with respect to Ptr4CL3 and Ptr4CL5 concentrations for the model without the complex.

<p>The first order sensitivity index for monolignol flux with respect to Ptr4CL3 and Ptr4CL5 concentrations for the model without the complex.</p