Joint And Individual Variation Explained Research Articles

Batch-effect correction in single-cell RNA sequencing data using JIVE.

In single-cell RNA sequencing analysis, addressing batch effects-technical artifacts stemming from factors such as varying sequencing technologies, equipment, and capture times-is crucial. These factors can cause unwanted variation and obfuscate the underlying biological signal of interest. The joint and individual variation explained (JIVE) method can be used to extract shared biological patterns from multi-source sequencing data while adjusting for individual non-biological variations (i.e. batch effect). However, its current implementation is originally designed for bulk sequencing data, making it computationally infeasible for large-scale single-cell sequencing datasets. In this study, we enhance JIVE for large-scale single-cell data by boosting its computational efficiency. Additionally, we introduce a novel application of JIVE for batch-effect correction on multiple single-cell sequencing datasets. Our enhanced method aims to decompose single-cell sequencing datasets into a joint structure capturing the true biological variability and individual structures, which capture technical variability within each batch. This joint structure is then suitable for use in downstream analyses. We benchmarked the results against four popular tools, Seurat v5, Harmony, LIGER, and Combat-seq, which were developed for this purpose. JIVE performed best in terms of preserving cell-type effects and in scenarios in which the batch sizes are balanced. The JIVE implementation used for this analysis can be found at https://github.com/oconnell-statistics-lab/scJIVE.

Can Gait Characteristics Be Represented by Physical Activity Measured with Wrist-Worn Accelerometers?

Wearable accelerometers allow for continuous monitoring of function and behaviors in the participant's naturalistic environment. Devices are typically worn in different body locations depending on the concept of interest and endpoint under investigation. The lumbar and wrist are commonly used locations: devices placed at the lumbar region enable the derivation of spatio-temporal characteristics of gait, while wrist-worn devices provide measurements of overall physical activity (PA). Deploying multiple devices in clinical trial settings leads to higher patient burden negatively impacting compliance and data quality and increases the operational complexity of the trial. In this work, we evaluated the joint information shared by features derived from the lumbar and wrist devices to assess whether gait characteristics can be adequately represented by PA measured with wrist-worn devices. Data collected at the Pfizer Innovation Research (PfIRe) Lab were used as a real data example, which had around 7 days of continuous at-home data from wrist- and lumbar-worn devices (GENEActiv) obtained from a group of healthy participants. The relationship between wrist- and lumbar-derived features was estimated using multiple statistical methods, including penalized regression, principal component regression, partial least square regression, and joint and individual variation explained (JIVE). By considering multilevel models, both between- and within-subject effects were taken into account. This work demonstrated that selected gait features, which are typically measured with lumbar-worn devices, can be represented by PA features measured with wrist-worn devices, which provides preliminary evidence to reduce the number of devices needed in clinical trials and to increase patients' comfort. Moreover, the statistical methods used in this work provided an analytic framework to compare repeated measures collected from multiple data modalities.

Brain structural co-development is associated with internalizing symptoms two years later in the ABCD cohort.

About 1/3 of youth spend more than four hours/day engaged in screen media activity (SMA). This investigation utilized longitudinal brain imaging and mediation analyses to examine relationships among SMA, brain patterns, and internalizing problems. Data from Adolescent Brain Cognitive Development (ABCD) participants with baseline and two-year follow-up structural imaging data that passed quality control (N = 5,166; 2,385 girls) were analyzed. Joint and Individual Variation Explained (JIVE) identified a brain co-development pattern among 221 brain features (i.e., differences in surface area, thickness, or cortical and subcortical gray-matter volume between baseline and two-year-follow-up data). Generalized linear mixed-effect models investigated associations between baseline SMA, structural co-development and internalizing and externalizing psychopathology at two-year follow-up. SMA at baseline was related to internalizing psychopathology at year 2 (β=0.020,SE=0.008,P=0.014) and a structural co-development pattern (β=0.015,SE=0.007,P=0.029), where the co-development pattern suggested that rates of change in gray-matter volumes of the brainstem, gray-matter volumes and/or cortical thickness measures of bilateral superior frontal, rostral middle frontal, inferior parietal, and inferior temporal regions were more similar than those in other regions. This component partially mediated the relationship between baseline SMA and future internalizing problems (indirect effect = 0.020, P-value = 0.043, proportion mediated: 2.24%). Greater youth engagement in SMA at ages 9-10 years statistically predicted higher levels of internalizing two years later. This association was mediated by cortical-brainstem circuitry, albeit with relatively small effect sizes. The findings may help delineate processes contributing to internalizing behaviors and assist in identifying individuals at greater risk for such problems.

Interpretive JIVE: Connections with CCA and an application to brain connectivity.

Joint and Individual Variation Explained (JIVE) is a model that decomposes multiple datasets obtained on the same subjects into shared structure, structure unique to each dataset, and noise. JIVE is an important tool for multimodal data integration in neuroimaging. The two most common algorithms are R.JIVE, an iterative approach, and AJIVE, which uses principal angle analysis. The joint structure in JIVE is defined by shared subspaces, but interpreting these subspaces can be challenging. In this paper, we reinterpret AJIVE as a canonical correlation analysis of principal component scores. This reformulation, which we call CJIVE, (1) provides an intuitive view of AJIVE; (2) uses a permutation test for the number of joint components; (3) can be used to predict subject scores for out-of-sample observations; and (4) is computationally fast. We conduct simulation studies that show CJIVE and AJIVE are accurate when the total signal ranks are correctly specified but, generally inaccurate when the total ranks are too large. CJIVE and AJIVE can still extract joint signal even when the joint signal variance is relatively small. JIVE methods are applied to integrate functional connectivity (resting-state fMRI) and structural connectivity (diffusion MRI) from the Human Connectome Project. Surprisingly, the edges with largest loadings in the joint component in functional connectivity do not coincide with the same edges in the structural connectivity, indicating more complex patterns than assumed in spatial priors. Using these loadings, we accurately predict joint subject scores in new participants. We also find joint scores are associated with fluid intelligence, highlighting the potential for JIVE to reveal important shared structure.

Brain structural covariation linked to screen media activity and externalizing behaviors in children.

Background and AimsScreen media activity (SMA) may impact neurodevelopment in youth. Cross-sectionally, SMA has been linked to brain structural patterns including cortical thinning in children. However, it remains unclear whether specific brain structural co-variation patterns are related to SMA and other clinically relevant measures such as psychopathology, cognition and sleep in children.MethodsAdolescent Brain Cognitive Development (ABCD) participants with useable baseline structural imaging (N = 10,691; 5,107 girls) were analyzed. We first used the Joint and Individual Variation Explained (JIVE) approach to identify cortical and subcortical covariation pattern(s) among a set of 221 brain features (i.e., surface area, thickness, or cortical and subcortical gray matter (GM) volumes). Then, the identified structural covariation pattern was used as a predictor in linear mixed-effect models to investigate its associations with SMA, psychopathology, and cognitive and sleep measures.ResultsA thalamus-prefrontal cortex (PFC)-brainstem structural co-variation pattern (circuit) was identified. The pattern suggests brainstem and bilateral thalamus proper GM volumes covary more strongly with GM volume and/or surface area in bilateral superior frontal gyral, rostral middle frontal, inferior parietal, and inferior temporal regions. This covariation pattern highly resembled one previously linked to alcohol use initiation prior to adulthood and was consistent in girls and boys. Subsequent regression analyses showed that this co-variation pattern associated with SMA (β = 0.107, P = 0.002) and externalizing psychopathology (β = 0.117, P = 0.002), respectively.Discussion and ConclusionsFindings linking SMA-related structural covariation to externalizing psychopathology in youth resonate with prior studies of alcohol-use initiation and suggest a potential neurodevelopmental mechanism underlying addiction vulnerability.

Metabolomic Characterization of Pigmented and Non-Pigmented Potato Cultivars Using a Joint and Individual Variation Explained (JIVE).

Potatoes (Solanum tuberosum L.) are one of the most valuable agricultural crops, and the flesh of these tubers provides various classes of healthy compounds important for human nutrition. This work presents the results of a joint analysis of different chemical classes of compounds which provided insights on the metabolic characterization of pigmented and non-pigmented potato varieties collected from Italy. The identification of common or individual metabolic characteristics across the omic datasets (antioxidants, total polyphenolic content, polyphenols, and sugars) is conducted by Joint and Individual Variation Explained (JIVE), a data fusion multivariate approach. The common part of the multivariate model allowed the separation between non-pigmented and pigmented samples. Polyphenolic compounds were mainly responsible for the separation between purple-fleshed and red-skinned potatoes. An additional detailed analysis of the anthocyanin composition, including the acylated anthocyanins, allowed to pinpoint the diversities between the pigmented potato groups. Furthermore, the presence of an appreciable amount of hydroxycinnamic acids and anthocyanins in the purple-fleshed varieties, which are also characterized by a lower content of sugars, is found. Our results provide scientific evidence for the promotion of promising potato cultivars, which are characterized by a remarkable amount of various health benefit compounds.

Multi-omics data integration for subtype identification of Chinese lower-grade gliomas: A joint similarity network fusion approach

Lower-grade gliomas (LGG), characterized by heterogeneity and invasiveness, originate from the central nervous system. Although studies focusing on molecular subtyping and molecular characteristics have provided novel insights into improving the diagnosis and therapy of LGG, there is an urgent need to identify new molecular subtypes and biomarkers that are promising to improve patient survival outcomes. Here, we proposed a joint similarity network fusion (Joint-SNF) method to integrate different omics data types to construct a fused network using the Joint and Individual Variation Explained (JIVE) technique under the SNF framework. Focusing on the joint network structure, a spectral clustering method was employed to obtain subtypes of patients. Simulation studies show that the proposed Joint-SNF method outperforms the original SNF approach under various simulation scenarios. We further applied the method to a Chinese LGG data set including mRNA expression, DNA methylation and microRNA (miRNA). Three molecular subtypes were identified and showed statistically significant differences in patient survival outcomes. The five-year mortality rates of the three subtypes are 80.8%, 32.1%, and 34.4%, respectively. After adjusting for clinically relevant covariates, the death risk of patients in Cluster 1 was 5.06 times higher than patients in other clusters. The fused network attained by the proposed Joint-SNF method enhances strong similarities, thus greatly improves subtyping performance compared to the original SNF method. The findings in the real application may provide important clues for improving patient survival outcomes and for precision treatment for Chinese LGG patients. An R package to implement the method can be accessed in Github at https://github.com/Sameerer/Joint-SNF.

Brain anatomical covariation patterns linked to binge drinking and age at first full drink

Binge drinking and age at first full drink (AFD) of alcohol prior to 21 years (AFD < 21) have been linked to neuroanatomical differences in cortical and subcortical grey matter (GM) volume, cortical thickness, and surface area. Despite the importance of understanding network-level relationships, structural covariation patterns among these morphological measures have yet to be examined in relation to binge drinking and AFD < 21. Here, we used the Joint and Individual Variance Explained (JIVE) method to characterize structural covariation patterns common across and specific to morphological measures in 293 participants (149 individuals with past-12-month binge drinking and 144 healthy controls) from the Human Connectome Project (HCP). An independent dataset (Nathan Kline Institute Rockland Sample; NKI-RS) was used to examine reproducibility/generalizability. We identified a reproducible joint component dominated by structural covariation between GM volume in the brainstem and thalamus proper, and GM volume and surface area in prefrontal cortical regions. Using linear mixed regression models, we found that participants with AFD < 21 showed lower joint component scores in both the HCP (beta = 0.059, p-value = 0.016; Cohen’s d = 0.441) and NKI-RS (beta = 0.023, p-value = 0.040, Cohen’s d = 0.216) datasets, whereas the individual thickness component associated with binge drinking (p-value = 0.02) and AFD < 21 (p-value < 0.001) in the HCP dataset was not statistically significant in the NKI-RS sample. Our findings were also generalizable to the HCP full sample (n = 880 participants). Taken together, our results show that use of JIVE analysis in high-dimensional, large-scale, psychiatry-related datasets led to discovery of a reproducible cortical and subcortical structural covariation pattern involving brain regions relevant to thalamic-PFC-brainstem neural circuitry which is related to AFD < 21 and suggests a possible extension of existing addiction neurocircuitry in humans.

Joint and Individual Representation of Domains of Physical Activity, Sleep, and Circadian Rhythmicity.

Developments in wearable technology have enabled researchers to continuously and objectively monitor various aspects and physiological domains of real-life including levels of physical activity, quality of sleep, and strength of circadian rhythm in many epidemiological and clinical studies. Current analytical practice is to summarize each of these three domains individually via a standard inventory of interpretable features, and explore individual associations between the features and clinical variables. However, the features often exhibit significant interaction and correlation both within and between domains. Integration of features across multiple domains remains methodologically challenging. To address this problem, we propose to use joint and individual variation explained (JIVE), a dimension reduction technique that efficiently deals with multivariate data representing multiple domains. In this paper, we review the most frequently used features to characterize the domains of physical activity, sleep, and circadian rhythniicity and illustrate the approach using wrist-worn actigraphy data from 198 participants of the Baltimore Longitudinal Study of Aging.

Multi-omic molecular profiling of lung cancer in COPD.

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.

Recovering Joint and Individual Components in Facial Data.

A set of images depicting faces with different expressions or in various ages consists of components that are shared across all images (i.e., joint components) imparting to the depicted object the properties of human faces as well as individual components that are related to different expressions or age groups. Discovering the common (joint) and individual components in facial images is crucial for applications such as facial expression transfer and age progression. The problem is rather challenging when dealing with images captured in unconstrained conditions in the presence of sparse non-Gaussian errors of large magnitude (i.e., sparse gross errors or outliers) and contain missing data. In this paper, we investigate the use of a method recently introduced in statistics, the so-called Joint and Individual Variance Explained (JIVE) method, for the robust recovery of joint and individual components in visual facial data consisting of an arbitrary number of views. Since the JIVE is not robust to sparse gross errors, we propose alternatives, which are (1) robust to sparse gross, non-Gaussian noise, (2) able to automatically find the individual components rank, and (3) can handle missing data. We demonstrate the effectiveness of the proposed methods to several computer vision applications, namely facial expression synthesis and 2D and 3D face age progression 'in-the-wild'.

JIVE integration of imaging and behavioral data

A major goal in neuroscience is to understand the neural pathways underlying human behavior. We introduce the recently developed Joint and Individual Variation Explained (JIVE) method to the neuroscience community to simultaneously analyze imaging and behavioral data from the Human Connectome Project. Motivated by recent computational and theoretical improvements in the JIVE approach, we simultaneously explore the joint and individual variation between and within imaging and behavioral data. In particular, we demonstrate that JIVE is an effective and efficient approach for integrating task fMRI and behavioral variables using three examples: one example where task variation is strong, one where task variation is weak and a reference case where the behavior is not directly related to the image. These examples are provided to visualize the different levels of signal found in the joint variation including working memory regions in the image data and accuracy and response time from the in-task behavioral variables. Joint analysis provides insights not available from conventional single block decomposition methods such as Singular Value Decomposition. Additionally, the joint variation estimated by JIVE appears to more clearly identify the working memory regions than Partial Least Squares (PLS), while Canonical Correlation Analysis (CCA) gives grossly overfit results. The individual variation in JIVE captures the behavior unrelated signals such as a background activation that is spatially homogeneous and activation in the default mode network. The information revealed by this individual variation is not examined in traditional methods such as CCA and PLS. We suggest that JIVE can be used as an alternative to PLS and CCA to improve estimation of the signal common to two or more datasets and reveal novel insights into the signal unique to each dataset.

Prediction With Dimension Reduction of Multiple Molecular Data Sources for Patient Survival

Predictive modeling from high-dimensional genomic data is often preceded by a dimension reduction step, such as principal component analysis (PCA). However, the application of PCA is not straightforward for multisource data, wherein multiple sources of ‘omics data measure different but related biological components. In this article, we use recent advances in the dimension reduction of multisource data for predictive modeling. In particular, we apply exploratory results from Joint and Individual Variation Explained (JIVE), an extension of PCA for multisource data, for prediction of differing response types. We conduct illustrative simulations to illustrate the practical advantages and interpretability of our approach. As an application example, we consider predicting survival for patients with glioblastoma multiforme from 3 data sources measuring messenger RNA expression, microRNA expression, and DNA methylation. We also introduce a method to estimate JIVE scores for new samples that were not used in the initial dimension reduction and study its theoretical properties; this method is implemented in the R package R.JIVE on CRAN, in the function jive.predict.

R.JIVE for exploration of multi-source molecular data.

: The integrative analysis of multiple high-throughput data sources that are available for a common sample set is an increasingly common goal in biomedical research. Joint and individual variation explained (JIVE) is a tool for exploratory dimension reduction that decomposes a multi-source dataset into three terms: a low-rank approximation capturing joint variation across sources, low-rank approximations for structured variation individual to each source and residual noise. JIVE has been used to explore multi-source data for a variety of application areas but its accessibility was previously limited. We introduce R.JIVE, an intuitive R package to perform JIVE and visualize the results. We discuss several improvements and extensions of the JIVE methodology that are included. We illustrate the package with an application to multi-source breast tumor data from The Cancer Genome Atlas. R.JIVE is available via the Comprehensive R Archive Network (CRAN) under the GPLv3 license: https://cran.r-project.org/web/packages/r.jive/ elock@umn.edu Supplementary data are available at Bioinformatics online.

Separating common from distinctive variation

BackgroundJoint and individual variation explained (JIVE), distinct and common simultaneous component analysis (DISCO) and O2-PLS, a two-block (X-Y) latent variable regression method with an integral OSC filter can all be used for the integrated analysis of multiple data sets and decompose them in three terms: a low(er)-rank approximation capturing common variation across data sets, low(er)-rank approximations for structured variation distinctive for each data set, and residual noise. In this paper these three methods are compared with respect to their mathematical properties and their respective ways of defining common and distinctive variation.ResultsThe methods are all applied on simulated data and mRNA and miRNA data-sets from GlioBlastoma Multiform (GBM) brain tumors to examine their overlap and differences. When the common variation is abundant, all methods are able to find the correct solution. With real data however, complexities in the data are treated differently by the three methods.ConclusionsAll three methods have their own approach to estimate common and distinctive variation with their specific strength and weaknesses. Due to their orthogonality properties and their used algorithms their view on the data is slightly different. By assuming orthogonality between common and distinctive, true natural or biological phenomena that may not be orthogonal at all might be misinterpreted.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1037-2) contains supplementary material, which is available to authorized users.

Analysis of multi-source metabolomic data using joint and individual variation explained (JIVE).

Metabolic profiling is increasingly being used for understanding biological processes but there is no single analytical technique that provides a complete quantitative or qualitative profiling of the metabolome. Data fusion (i.e. joint analysis of data from multiple sources) has the potential to circumvent this issue facilitating knowledge discovery and reliable biomarker identification. Another field of application of data fusion is the simultaneous analysis of metabolomic changes through several biofluids or tissues. However, metabolomics typically deals with large datasets, with hundreds to thousands of variables and the identification of shared and individual factors or structures across multiple sources is challenging due to the high variable to sample ratios and differences in intensity and noise range. In this work we apply a recent method, Joint and Individual Variation Explained (JIVE), for the integrated unsupervised analysis of metabolomic profiles from multiple data sources. This method separates the shared patterns among data sources (i.e. the joint structure) from the individual structure of each data source that is unrelated to the joint structure. Two examples are described to show the applicability of JIVE for the simultaneous analysis of multi-source data using: (i) plasma samples subjected to different analytical techniques, sample treatment and measurement conditions; and (ii) plasma and urine samples subjected to liquid chromatography-mass spectrometry measured using two ionization conditions.

JOINT AND INDIVIDUAL VARIATION EXPLAINED (JIVE) FOR INTEGRATED ANALYSIS OF MULTIPLE DATA TYPES.

Research in several fields now requires the analysis of datasets in which multiple high-dimensional types of data are available for a common set of objects. In particular, The Cancer Genome Atlas (TCGA) includes data from several diverse genomic technologies on the same cancerous tumor samples. In this paper we introduce Joint and Individual Variation Explained (JIVE), a general decomposition of variation for the integrated analysis of such datasets. The decomposition consists of three terms: a low-rank approximation capturing joint variation across data types, low-rank approximations for structured variation individual to each data type, and residual noise. JIVE quantifies the amount of joint variation between data types, reduces the dimensionality of the data, and provides new directions for the visual exploration of joint and individual structure. The proposed method represents an extension of Principal Component Analysis and has clear advantages over popular two-block methods such as Canonical Correlation Analysis and Partial Least Squares. A JIVE analysis of gene expression and miRNA data on Glioblastoma Multiforme tumor samples reveals gene-miRNA associations and provides better characterization of tumor types.

Joint and individual variation explained (JIVE) for integrated analysis of multiple data types

Joint and individual variation explained (JIVE) for integrated analysis of multiple data types