Search bioRxiv⌕ Search

bioRxiv · 10.1101/2024.01.15.575678

A Distributed Computing Solution for Privacy-Preserving Genome-Wide Association Studies

Abstract

Breakthroughs in sequencing technologies led to an exponential growth of genomic data, providing unprecedented biological in-sights and new therapeutic applications. However, analyzing such large amounts of sensitive data raises key concerns regarding data privacy, specifically when the information is outsourced to third-party infrastructures for data storage and processing (e.g., cloud computing). Current solutions for data privacy protection resort to centralized designs or cryptographic primitives that impose considerable computational overheads, limiting their applicability to large-scale genomic analysis. We introduce GO_SCPLOWYOSAC_SCPLOW, a secure and privacy-preserving distributed genomic analysis solution. Unlike in previous work, GO_SCPLOWYOSAC_SCPLOW follows a distributed processing design that enables handling larger amounts of genomic data in a scalable and efficient fashion. Further, by leveraging trusted execution environments (TEEs), namely Intel SGX, GO_SCPLOWYOSAC_SCPLOW allows users to confidentially delegate their GWAS analysis to untrusted third-party infrastructures. To overcome the memory limitations of SGX, we implement a computation partitioning scheme within GO_SCPLOWYOSAC_SCPLOW. This scheme reduces the number of operations done inside the TEEs while safeguarding the users genomic data privacy. By integrating this security scheme in Glow, GO_SCPLOWYOSAC_SCPLOW provides a secure and distributed environment that facilitates diverse GWAS studies. The experimental evaluation validates the applicability and scalability of GO_SCPLOWYOSAC_SCPLOW, reinforcing its ability to provide enhanced security guarantees. Further, the results show that, by distributing GWASes computations, one can achieve a practical and usable privacy-preserving solution.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Brito, C., Paulo, J., Ferreira, P. G.. 2024-01-16. A Distributed Computing Solution for Privacy-Preserving Genome-Wide Association Studies. https://doi.org/10.1101/2024.01.15.575678

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Uncovering Viral Signals Across Cell Populations in Colorectal Cancer

Viral sequences have been detected in colorectal cancer, but their cellular and anatomical distribution remains poorly resolved. We aimed to establish a cell-type-resolved map of viral reference-associated RNA signals across colorectal cancer, tumour-adjacent normal tissue, and healthy colon. We repurposed human-unmapped reads from single-cell RNA sequencing libraries generated in ten publicly available studies. We retained cell-barcode and unique molecular identifier information, removed duplicate molecules, and aligned reads to a curated human-associated viral reference using three aligners. Viral signals were analysed across cell types, tissue conditions, and colorectal segments. We used participant-grouped repeated cross-validation to evaluate tissue-condition classification and screened an independent paired colorectal cancer proteomics cohort for compatible peptide matches. The study included 547 libraries from 112 participants, including 49 with matched colorectal cancer and tumour-adjacent normal samples, and approximately 415,000 cells spanning ten major cell populations. Viral reference-associated RNA signals differed across epithelial, immune, stromal, and vascular compartments, tissue conditions, and anatomical regions of the colon. Of 318 independent healthy-reference viral-load comparisons, seven involving six virus-cell-type groups remained significant after Benjamini-Hochberg correction, including plasma-cell HHV-7 and HHV-6B and mast-cell HCV-2. Cell-type-resolved viral features distinguished colorectal cancer, tumour-adjacent normal tissue, and healthy colon in participant-grouped validation; random forest achieved a macro-AUC of 0.957 (SD 0.028), with HERV-K113 as the leading quantitative feature. An independent proteomic screen identified peptide matches compatible with 20 candidate viral groups. We established a cell-type-resolved map of viral reference-associated RNA signals across colorectal tissue conditions and anatomical regions. By identifying candidate viral signals in epithelial and immune compartments, this map provides a basis for investigating virus-host pathways involved in tumour biology, immune regulation, and antigen-presentation states, and could help prioritise future combination strategies pairing virus-directed or virus-mimetic approaches with standard treatment or immune checkpoint blockade.

bioinformatics↗

Statistical significance testing for spatial domain detection in spatial transcriptomics

In spatial transcriptomics, domain-detection methods group platform-specific spatial measurement units--cells, bins or multicellular spots--into spatial domains for comparing molecular programs, cellular composition and interactions among tissue regions. However, the number of candidate domains detected in the same tissue can vary with user-specified parameters or model-selection criteria. Whether candidate domains should be merged can be framed as a test of a single-domain null hypothesis, under which each gene has constant mean expression across all spatial units in the combined region. However, testing candidate domains on the same gene-expression data used to detect them may induce post-selection bias and yield anti-conservative p-values, increasing the risk of oversegmentation. To address these challenges, we introduce SigDoTS (statistical Significance testing for Domain deTection in Spatial transcriptomics), a hypothesis-testing framework for spatial domain detection. SigDoTS uses hierarchical testing to determine which candidate domains to retain or merge, with adjustment for family-wise error control. It accounts for gene-gene covariance and spatial dependence and computes p-values by rerunning the upstream domain-detection pipeline on datasets simulated under the fitted single-domain null. In simulations, SigDoTS controlled the type I error rate at the root node under the single-domain null and improved recovery of the true spatial domains when multiple domains were present. In human dorsolateral prefrontal cortex, SigDoTS retained superficial and deep Layer 6 domains but merged Layer 3 candidate domains across different initial numbers of candidate domains. In ovarian and colorectal cancers, SigDoTS retained epithelial domains with different gene-expression programs and local immune environments, together with immune, stromal and vascular domains.

bioinformatics↗

ASD Neuro Agentic (ANA): An Agentic Framework for Feature Discovery and Cross Site Generalization in Autism fMRI Classification

Classifiers of autism spectrum disorder (ASD) from resting state functional MRI rarely generalize across sites, and many reported accuracies are inflated by data leakage.We show that an agentic artificial intelligence framework, ASD Neuro Agentic (ANA), whose language model agents propose features from the literature and researcher input while fixed tools perform every calculation, can search auditably for site independent classifiers while controlling the leakage. In 1,028 participants from 17 ABIDE I centers, ANA tested 71 pipelines and selected a ComBat harmonized ensemble of tangent space connectivity models from six parcellations and 98 public connectivity derivatives. In leave one center out testing, the ensemble reached an area under the curve of 0.814 (95% CI, 0.773 to 0.841), outperforming ASD DiagNet and ASD SAENet. Predictive connectivity was mainly reduced in ASD. Agentic AI offers a systematic and efficient approach to exploring, evaluating, and identifying pipelines as model selection grows complex.

bioinformatics↗