More Like this

1. Accurate flux predictions using tissue-specific gene expression in plant metabolic modeling

   https://doi.org/10.1093/bioinformatics/btad186  

   Kaste, Joshua A; Shachar-Hill, Yair (May 2023, Bioinformatics)

   Birol, Inanc (Ed.)

   Abstract Motivation The accurate prediction of complex phenotypes such as metabolic fluxes in living systems is a grand challenge for systems biology and central to efficiently identifying biotechnological interventions that can address pressing industrial needs. The application of gene expression data to improve the accuracy of metabolic flux predictions using mechanistic modeling methods such as flux balance analysis (FBA) has not been previously demonstrated in multi-tissue systems, despite their biotechnological importance. We hypothesized that a method for generating metabolic flux predictions informed by relative expression levels between tissues would improve prediction accuracy. Results Relative gene expression levels derived from multiple transcriptomic and proteomic datasets were integrated into FBA predictions of a multi-tissue, diel model of Arabidopsis thaliana’s central metabolism. This integration dramatically improved the agreement of flux predictions with experimentally based flux maps from 13C metabolic flux analysis compared with a standard parsimonious FBA approach. Disagreement between FBA predictions and MFA flux maps was measured using weighted averaged percent error values, and for parsimonious FBA this was169%–180% for high light conditions and 94%–103% for low light conditions, depending on the gene expression dataset used. This fell to 10%-13% and 9%-11% upon incorporating expression data into the modeling process, which also substantially altered the predicted carbon and energy economy of the plant. Availability and implementation Code and data generated as part of this study are available from https://github.com/Gibberella/ArabidopsisGeneExpressionWeights. 

   more » « less
2. Generalizing Graph ODE for Learning Complex System Dynamics across Environments

   https://doi.org/10.1145/3580305.3599362  

   Huang, Zijie; Sun, Yizhou; Wang, Wei (August 2023, Proceedings of the 29th ACM SIGKDD Conference on Knowledge Discovery and Data Mining (KDD ’23))

   Learning multi-agent system dynamics has been extensively studied for various real-world applications, such as molecular dynamics in biology, multi-body system in physics, and particle dynamics in material science. Most of the existing models are built to learn single system dynamics, which learn the dynamics from observed historical data and predict the future trajectory. In practice, however, we might observe multiple systems that are generated across different environments, which differ in latent exogenous factors such as temperature and gravity. One simple solution is to learn multiple environment-specific models, but it fails to exploit the potential commonalities among the dynamics across environments and offers poor prediction results where per-environment data is sparse or limited. Here, we present GG-ODE (Generalized Graph Ordinary Differential Equations), a machine learning framework for learning continuous multi-agent system dynamics across environments. Our model learns system dynamics using neural ordinary differential equations (ODE) parameterized by Graph Neural Networks (GNNs) to capture the continuous interaction among agents. We achieve the model generalization by assuming the dynamics across different environments are governed by common physics laws that can be captured via learning a shared ODE function. The distinct latent exogenous factors learned for each environment are incorporated into the ODE function to account for their differences. To improve model performance, we additionally design two regularization losses to (1) enforce the orthogonality between the learned initial states and exogenous factors via mutual information minimization; and (2) reduce the temporal variance of learned exogenous factors within the same system via contrastive learning. Experiments over various physical simulations show that our model can accurately predict system dynamics, especially in the long range, and can generalize well to new systems with few observations. 

   more » « less
3. Network-based multi-task learning models for biomarker selection and cancer outcome prediction

   https://doi.org/10.1093/bioinformatics/btz809  

   Wang, Zhibo; He, Zhezhi; Shah, Milan; Zhang, Teng; Fan, Deliang; Zhang, Wei; Cowen, Lenore (November 2019, Bioinformatics)

   Abstract Motivation Detecting cancer gene expression and transcriptome changes with mRNA-sequencing (RNA-Seq) or array-based data are important for understanding the molecular mechanisms underlying carcinogenesis and cellular events during cancer progression. In previous studies, the differentially expressed genes were detected across patients in one cancer type. These studies ignored the role of mRNA expression changes in driving tumorigenic mechanisms that are either universal or specific in different tumor types. To address the problem, we introduce two network-based multi-task learning frameworks, NetML and NetSML, to discover common differentially expressed genes shared across different cancer types as well as differentially expressed genes specific to each cancer type. The proposed frameworks consider the common latent gene co-expression modules and gene-sample biclusters underlying the multiple cancer datasets to learn the knowledge crossing different tumor types. Results Large-scale experiments on simulations and real cancer high-throughput datasets validate that the proposed network-based multi-task learning frameworks perform better sample classification compared with the models without the knowledge sharing across different cancer types. The common and cancer specific molecular signatures detected by multi-task learning frameworks on TCGA ovarian cancer, breast cancer, and prostate cancer datasets are correlated with the known marker genes and enriched in cancer relevant KEGG pathways and Gene Ontology terms. Availability and Implementation Source code is available at: https://github.com/compbiolabucf/NetML Supplementary information Supplementary data are available at Bioinformatics 

   more » « less
4. DNR: A Tunable Robust Pruning Framework Through Dynamic Network Rewiring of DNNs

   Kundu, Souvik; Nazemi, Mahdi; Beerel, Peter A; Pedram, Massoud (January 2021, 26th Asia and South Pacific Design Automation Conference)

   null (Ed.)

   This paper presents a dynamic network rewiring (DNR) method to generate pruned deep neural network (DNN) models that are robust against adversarial attacks yet maintain high accuracy on clean im- ages. In particular, the disclosed DNR method is based on a unified constrained optimization formulation using a hybrid loss function that merges ultra-high model compression with robust adversar- ial training. This training strategy dynamically adjusts inter-layer connectivity based on per-layer normalized momentum computed from the hybrid loss function. In contrast to existing robust pruning frameworks that require multiple training iterations, the proposed learning strategy achieves an overall target pruning ratio with only a single training iteration and can be tuned to support both irregu- lar and structured channel pruning. To evaluate the merits of DNR, experiments were performed with two widely accepted models, namely VGG16 and ResNet-18, on CIFAR-10, CIFAR-100 as well as with VGG16 on Tiny-ImageNet. Compared to the baseline un- compressed models, DNR provides over 20× compression on all the datasets with no significant drop in either clean or adversarial classification accuracy. Moreover, our experiments show that DNR consistently finds compressed models with better clean and adver- sarial image classification performance than what is achievable through state-of-the-art alternatives. Our models and test codes are available at https://github.com/ksouvik52/DNR_ASP_DAC2021. 

   more » « less
5. Parameter estimation and forecasting with quantified uncertainty for ordinary differential equation models using QuantDiffForecast : A MATLAB toolbox and tutorial

   https://doi.org/10.1002/sim.10036  

   Chowell, Gerardo; Bleichrodt, Amanda; Luo, Ruiyan (February 2024, Statistics in Medicine)

   Mathematical models based on systems of ordinary differential equations (ODEs) are frequently applied in various scientific fields to assess hypotheses, estimate key model parameters, and generate predictions about the system's state. To support their application, we present a comprehensive, easy‐to‐use, and flexible MATLAB toolbox,QuantDiffForecast, and associated tutorial to estimate parameters and generate short‐term forecasts with quantified uncertainty from dynamical models based on systems of ODEs. We provide software (https://github.com/gchowell/paramEstimation_forecasting_ODEmodels/) and detailed guidance on estimating parameters and forecasting time‐series trajectories that are characterized using ODEs with quantified uncertainty through a parametric bootstrapping approach. It includes functions that allow the user to infer model parameters and assess forecasting performance for different ODE models specified by the user, using different estimation methods and error structures in the data. The tutorial is intended for a diverse audience, including students training in dynamic systems, and will be broadly applicable to estimate parameters and generate forecasts from models based on ODEs. The functions included in the toolbox are illustrated using epidemic models with varying levels of complexity applied to data from the 1918 influenza pandemic in San Francisco. A tutorial video that demonstrates the functionality of the toolbox is included. 

   more » « less