Breast cancer remains a significant global health challenge due to its complexity, which arises from multiple genetic and epigenetic mutations that originate in normal breast tissue. Traditional machine learning models often fall short in addressing the intricate gene interactions that complicate drug design and treatment strategies. In contrast, our study introduces GEMDiff, a novel computational workflow leveraging a diffusion model to bridge the gene expression states between normal and tumor conditions. GEMDiff augments RNAseq data and simulates perturbation transformations between normal and tumor gene states, enhancing biomarker identification. GEMDiff can handle large-scale gene expression data without succumbing to the scalability and stability issues that plague other generative models. By avoiding the need for task-specific hyper-parameter tuning and specific loss functions, GEMDiff can be generalized across various tasks, making it a robust tool for gene expression analysis. The model's ability to augment RNA-seq data and simulate gene perturbations provides a valuable tool for researchers. This capability can be used to generate synthetic data for training other machine learning models, thereby addressing the issue of limited biological data and enhancing the performance of predictive models. The effectiveness of GEMDiff is demonstrated through a case study using breast mRNA gene expression data, identifying 307 core genes involved in the transition from a breast tumor to a normal gene expression state. GEMDiff is open source and available at https://github.com/xai990/GEMDiff.git under the MIT license.

The recent COVID-19 crisis has demonstrated the potential of cutting-edge genomics research. However, privacy of these sensitive pieces of information is an area of significant concern for health professionals and genomics researchers. The current security model depends on securing location and data transmission channels but lacks the needed flexibility. Even when data is encrypted, key distribution and access control to those keys can be complex, leading to complex systems and reduced research productivity. In this work, we investigate an attribute-based access control model for genomics data. This work builds on top of a Named Data Networking (NDN) Name-based Access Control (NAC) model and explores how attribute-based encryption can be used to provide access control.

The COVID-19 crisis and the subsequent vaccine development have demonstrated the potential of cutting-edge genomics research. However, the privacy of these sensitive pieces of information is an area of significant concern for genomics researchers. The current security models make it difficult to create flexible, automated, and secure data-sharing frameworks. These models also increase the complexity of adding or revoking access.

Gene co-expression networks (GCNs) provide multiple benefits to molecular research including hypothesis generation and biomarker discovery. Transcriptome profiles serve as input for GCN construction and are derived from increasingly larger studies with samples across multiple experimental conditions, treatments, time points, genotypes, etc. Such experiments with larger numbers of variables confound discovery of true network edges, exclude edges and inhibit discovery of context (or condition) specific network edges. To demonstrate this problem, a 475-sample dataset is used to show that up to 97% of GCN edges can be misleading because correlations are false or incorrect. False and incorrect correlations can occur when tests are applied without ensuring assumptions are met, and pairwise gene expression may not meet test assumptions if the expression of at least one gene in the pairwise comparison is a function of multiple confounding variables. The 'one-size-fits-all' approach to GCN construction is therefore problematic for large, multivariable datasets. Recently, the Knowledge Independent Network Construction toolkit has been used in multiple studies to provide a dynamic approach to GCN construction that ensures statistical tests meet assumptions and confounding variables are addressed. Additionally, it can associate experimental context for each edge of the network resulting in context-specific GCNs (csGCNs). To help researchers recognize such challenges in GCN construction, and the creation of csGCNs, we provide a review of the workflow.

BACKGROUND: Quantification of gene expression from RNA-seq data is a prerequisite for transcriptome analysis such as differential gene expression analysis and gene co-expression network construction. Individual RNA-seq experiments are larger and combining multiple experiments from sequence repositories can result in datasets with thousands of samples. Processing hundreds to thousands of RNA-seq data can result in challenges related to data management, access to sufficient computational resources, navigation of high-performance computing (HPC) systems, installation of required software dependencies, and reproducibility. Processing of larger and deeper RNA-seq experiments will become more common as sequencing technology matures. RESULTS: GEMmaker, is a nf-core compliant, Nextflow workflow, that quantifies gene expression from small to massive RNA-seq datasets. GEMmaker ensures results are highly reproducible through the use of versioned containerized software that can be executed on a single workstation, institutional compute cluster, Kubernetes platform or the cloud. GEMmaker supports popular alignment and quantification tools providing results in raw and normalized formats. GEMmaker is unique in that it can scale to process thousands of local or remote stored samples without exceeding available data storage. CONCLUSIONS: Workflows that quantify gene expression are not new, and many already address issues of portability, reusability, and scale in terms of access to CPUs. GEMmaker provides these benefits and adds the ability to scale despite low data storage infrastructure. This allows users to process hundreds to thousands of RNA-seq samples even when data storage resources are limited. GEMmaker is freely available and fully documented with step-by-step setup and execution instructions.

Gene Co-expression Network (GCN) analysis is a method to characterize the complexity underlying biological systems. With an increasing availability of datasets available for mining complex gene expression patterns, novel algorithms and computational frameworks must be developed to take advantage of the wealth of information. OSG-KINC is a Pegasus workflow that enables highly parallel execution of KINC - Knowledge Independent Network Construction - using resources available on the Open Science Grid (OSG). A yeast GCN was constructed using the OSG-KINC workflow, providing an example GCN resource for biological hypothesis testing. Timing experiments demonstrate that the number of jobs submitted by the user significantly affects the performance of the workflow. An overview of workflow usage, bottlenecks, and efforts for improvement is provided. OSG-KINC is freely available at https://github.com/feltus/OSG-KINC under GNU General Public License version 3.

Motivation: The ability to centralize and store data for long periods on an end user's computational resources is increasingly difficult for many scientific disciplines. For example, genomics data is increasingly large and distributed, and the data needs to be moved into workflow execution sites ranging from lab workstations to the cloud. However, the typical user is not always informed on emerging network technology or the most efficient methods to move and share data. Thus, the user defaults to using inefficient methods for transfer across the commercial internet. Results: To accelerate large data transfer, we created a tool called the Big Data Smart Socket (BDSS) that abstracts data transfer methodology from the user. The user provides BDSS with a manifest of datasets stored in a remote storage repository. BDSS then queries a metadata repository for curated data transfer mechanisms and optimal path to move each of the files in the manifest to the site of workflow execution. BDSS functions as a standalone tool or can be directly integrated into a computational workflow such as provided by the Galaxy Project. To demonstrate applicability, we use BDSS within a biological context, although it is applicable to any scientific domain. Availability and Implementation: BDSS is available under version 2 of the GNU General Public License at https://github.com/feltus/BDSS . Contact: [email protected].

Identification of genes and pathways involving in diseases and physiological conditions is a major task in systems biology. In this study, we develop a new non-parameter Ising model to integrate protein-protein interaction network and microarray data for identifying differentially expressed (DE) genes. We also propose a simulated annealing algorithm to find the optimal configuration of the Ising model. We test the Ising model to two breast cancer microarray data sets. The results show that more cancer related differentially expressed subnetworks and genes are identified by the Ising model than by the Markov random filed (MRF) model.