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The analysis of spatially resolved transcriptome enables the understanding of the spatial interactions between the cellular environment and transcriptional regulation. In particular, the characterization of the gene–gene co-expression at distinct spatial locations or cell types in the tissue enables delineation of spatial co-regulatory patterns as opposed to standard differential single gene analyses. To enhance the ability and potential of spatial transcriptomics technologies to drive biological discovery, we develop a statistical framework to detect gene co-expression patterns in a spatially structured tissue consisting of different clusters in the form of cell classes or tissue domains.

We develop SpaceX (spatially dependent gene co-expression network), a Bayesian methodology to identify both shared and cluster-specific co-expression network across genes. SpaceX uses an over-dispersed spatial Poisson model coupled with a high-dimensional factor model which is based on a dimension reduction technique for computational efficiency. We show via simulations, accuracy gains in co-expression network estimation and structure by accounting for (increasing) spatial correlation and appropriate noise distributions. In-depth analysis of two spatial transcriptomics datasets in mouse hypothalamus and human breast cancer using SpaceX, detected multiple hub genes which are related to cognitive abilities for the hypothalamus data and multiple cancer genes (e.g. collagen family) frommore »the tumor region for the breast cancer data.

The SpaceX R-package is available at github.com/bayesrx/SpaceX.

Supplementary data are available at Bioinformatics online.

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Graphical models are powerful tools that are regularly used to investigate complex dependence structures in high-throughput biomedical datasets. They allow for holistic, systems-level view of the various biological processes, for intuitive and rigorous understanding and interpretations. In the context of large networks, Bayesian approaches are particularly suitable because it encourages sparsity of the graphs, incorporate prior information, and most importantly account for uncertainty in the graph structure. These features are particularly important in applications with limited sample size, including genomics and imaging studies. In this paper, we review several recently developed techniques for the analysis of large networks under non-standard settings, including but not limited to, multiple graphs for data observed from multiple related subgroups, graphical regression approaches used for the analysis of networks that change with covariates, and other complex sampling and structural settings. We also illustrate the practical utility of some of these methods using examples in cancer genomics and neuroimaging.

With only 536 COVID-19 cases and 11 fatalities, India took the historic decision of a 21-day national lockdown on March 25, 2020. The lockdown was first extended to May 3 soon after the analysis of this article was completed, and then to May 18 while this article was being revised. In this article, we use a Bayesian extension of the susceptible-infected-removed (eSIR) model designed for intervention forecasting to study the short- and long-term impact of an initial 21-day lockdown on the total number of COVID-19 infections in India compared to other, less severe nonpharmaceutical interventions. We compare effects of hypothetical durations of lockdown on reducing the number of active and new infections. We find that the lockdown, if implemented correctly, can reduce the total number of cases in the short term, and buy India invaluable time to prepare its health care and disease-monitoring system. Our analysis shows we need to have some measures of suppression in place after the lockdown for increased benefit (as measured by reduction in the number of cases). A longer lockdown from 42–56 days is preferable to substantially ‘flatten the curve’ when compared to 21–28 days of lockdown. Our models focus solely on projecting the numbermore »of COVID-19 infections and thus inform policymakers about one aspect of this multifaceted decision-making problem. We conclude with a discussion on the pivotal role of increased testing, reliable and transparent data, proper uncertainty quantification, accurate interpretation of forecasting models, reproducible data science methods, and tools that can enable data-driven policymaking during a pandemic. Our software products are available at covind19.org.« less

We propose a curve-based Riemannian geometric approach for general shape-based statistical analyses of tumours obtained from radiologic images. A key component of the framework is a suitable metric that enables comparisons of tumour shapes, provides tools for computing descriptive statistics and implementing principal component analysis on the space of tumour shapes and allows for a rich class of continuous deformations of a tumour shape. The utility of the framework is illustrated through specific statistical tasks on a data set of radiologic images of patients diagnosed with glioblastoma multiforme, a malignant brain tumour with poor prognosis. In particular, our analysis discovers two patient clusters with very different survival, subtype and genomic characteristics. Furthermore, it is demonstrated that adding tumour shape information to survival models containing clinical and genomic variables results in a significant increase in predictive power.

Personalized (patient-specific) approaches have recently emerged with a precision medicine paradigm that acknowledges the fact that molecular pathway structures and activity might be considerably different within and across tumors. The functional cancer genome and proteome provide rich sources of information to identify patient-specific variations in signaling pathways and activities within and across tumors; however, current analytic methods lack the ability to exploit the diverse and multi-layered architecture of these complex biological networks. We assessed pan-cancer pathway activities for >7700 patients across 32 tumor types from The Cancer Proteome Atlas by developing a personalized cancer-specific integrated network estimation (PRECISE) model. PRECISE is a general Bayesian framework for integrating existing interaction databases, data-drivende novocausal structures, and upstream molecular profiling data to estimate cancer-specific integrated networks, infer patient-specific networks and elicit interpretable pathway-level signatures. PRECISE-based pathway signatures, can delineate pan-cancer commonalities and differences in proteomic network biology within and across tumors, demonstrates robust tumor stratification that is both biologically and clinically informative and superior prognostic power compared to existing approaches. Towards establishing the translational relevance of the functional proteome in research and clinical settings, we provide an online, publicly available, comprehensive database and visualization repository of our findings (https://mjha.shinyapps.io/PRECISE/).

Differential network analysis is an important way to understand network rewiring involved in disease progression and development. Building differential networks from multiple ‘omics data provides insight into the holistic differences of the interactive system under different patient-specific groups. DINGO was developed to infer group-specific dependencies and build differential networks. However, DINGO and other existing tools are limited to analyze data arising from a single platform, and modeling each of the multiple ‘omics data independently does not account for the hierarchical structure of the data.

We developed the iDINGO R package to estimate group-specific dependencies and make inferences on the integrative differential networks, considering the biological hierarchy among the platforms. A Shiny application has also been developed to facilitate easier analysis and visualization of results, including integrative differential networks and hub gene identification across platforms.

R package is available on CRAN (https://cran.r-project.org/web/packages/iDINGO) and Shiny application at https://github.com/MinJinHa/iDINGO.

Supplementary data are available at Bioinformatics online.