Cancer survival prediction is important for developing personalized treatments and inducing disease-causing mechanisms. Multi-omics data integration is attracting widespread interest in cancer research for providing information for understanding cancer progression at multiple genetic levels. Many works, however, are limited because of the high dimensionality and heterogeneity of multi-omics data. In this paper, we propose a novel method to integrate multi-omics data for cancer survival prediction, called Stacked AutoEncoder-based Survival Prediction Neural Network (SAEsurv-net). In the cancer survival prediction for TCGA cases, SAEsurv-net addresses the curse of dimensionality with a two-stage dimensionality reduction strategy and handles multi-omics heterogeneity with a stacked autoencoder model. The two-stage dimensionality reduction strategy achieves a balance between computation complexity and information exploiting. The stacked autoencoder model removes most heterogeneities such as data's type and size in the first group of autoencoders, and integrates multiple omics data in the second autoencoder. The experiments show that SAEsurv-net outperforms models based on a single type of data as well as other state-of-the-art methods.
Cancer is a complex disease with significant social and economic impact. Advancements in high-throughput molecular assays and the reduced cost for performing high-quality multi-omics measurements have fuelled insights through machine learning . Previous studies have shown promise on using multiple omic layers to predict survival and stratify cancer patients. In this paper, we developed a Supervised Autoencoder (SAE) model for survival-based multi-omic integration which improves upon previous work, and report a Concrete Supervised Autoencoder model (CSAE), which uses feature selection to jointly reconstruct the input features as well as predict survival. Our experiments show that our models outperform or are on par with some of the most commonly used baselines, while either providing a better survival separation (SAE) or being more interpretable (CSAE). We also perform a feature selection stability analysis on our models and notice that there is a power-law relationship with features which are commonly associated with survival. The code for this project is available at: https://github.com/phcavelar/coxae
Recent advances in multimodal single-cell technologies have enabled simultaneous acquisitions of multiple omics data from the same cell, providing deeper insights into cellular states and dynamics. However, it is challenging to learn the joint representations from the multimodal data, model the relationship between modalities, and, more importantly, incorporate the vast amount of single-modality datasets into the downstream analyses. To address these challenges and correspondingly facilitate multimodal single-cell data analyses, three key tasks have been introduced: $\textit{modality prediction}$, $\textit{modality matching}$ and $\textit{joint embedding}$. In this work, we present a general Graph Neural Network framework $\textit{scMoGNN}$ to tackle these three tasks and show that $\textit{scMoGNN}$ demonstrates superior results in all three tasks compared with the state-of-the-art and conventional approaches. Our method is an official winner in the overall ranking of $\textit{Modality prediction}$ from NeurIPS 2021 Competition, and all implementations of our methods have been integrated into DANCE package~\url{https://github.com/OmicsML/dance}.
Empirically observed time series in physics, biology, or medicine, are commonly generated by some underlying dynamical system (DS) which is the target of scientific interest. There is an increasing interest to harvest machine learning methods to reconstruct this latent DS in a data-driven, unsupervised way. In many areas of science it is common to sample time series observations from many data modalities simultaneously, e.g. electrophysiological and behavioral time series in a typical neuroscience experiment. However, current machine learning tools for reconstructing DSs usually focus on just one data modality. Here we propose a general framework for multi-modal data integration for the purpose of nonlinear DS reconstruction and the analysis of cross-modal relations. This framework is based on dynamically interpretable recurrent neural networks as general approximators of nonlinear DSs, coupled to sets of modality-specific decoder models from the class of generalized linear models. Both an expectation-maximization and a variational inference algorithm for model training are advanced and compared. We show on nonlinear DS benchmarks that our algorithms can efficiently compensate for too noisy or missing information in one data channel by exploiting other channels, and demonstrate on experimental neuroscience data how the algorithm learns to link different data domains to the underlying dynamics.
Named entity disambiguation (NED), which involves mapping textual mentions to structured entities, is particularly challenging in the medical domain due to the presence of rare entities. Existing approaches are limited by the presence of coarse-grained structural resources in biomedical knowledge bases as well as the use of training datasets that provide low coverage over uncommon resources. In this work, we address these issues by proposing a cross-domain data integration method that transfers structural knowledge from a general text knowledge base to the medical domain. We utilize our integration scheme to augment structural resources and generate a large biomedical NED dataset for pretraining. Our pretrained model with injected structural knowledge achieves state-of-the-art performance on two benchmark medical NED datasets: MedMentions and BC5CDR. Furthermore, we improve disambiguation of rare entities by up to 57 accuracy points.
Schema matching is a core task of any data integration process. Being investigated in the fields of databases, AI, Semantic Web and data mining for many years, the main challenge remains the ability to generate quality matches among data concepts (e.g., database attributes). In this work, we examine a novel angle on the behavior of humans as matchers, studying match creation as a process. We analyze the dynamics of common evaluation measures (precision, recall, and f-measure), with respect to this angle and highlight the need for unbiased matching to support this analysis. Unbiased matching, a newly defined concept that describes the common assumption that human decisions represent reliable assessments of schemata correspondences, is, however, not an inherent property of human matchers. In what follows, we design PoWareMatch that makes use of a deep learning mechanism to calibrate and filter human matching decisions adhering the quality of a match, which are then combined with algorithmic matching to generate better match results. We provide an empirical evidence, established based on an experiment with more than 200 human matchers over common benchmarks, that PoWareMatch predicts well the benefit of extending the match with an additional correspondence and generates high quality matches. In addition, PoWareMatch outperforms state-of-the-art matching algorithms.
The occurrence and distributions of wildlife populations and communities are shifting as a result of global changes. To evaluate whether these shifts are negatively impacting biodiversity processes, it is critical to monitor the status, trends, and effects of environmental variables on entire communities. However, modeling the dynamics of multiple species simultaneously can require large amounts of diverse data, and few modeling approaches exist to simultaneously provide species and community level inferences. We present an "integrated community occupancy model" (ICOM) that unites principles of data integration and hierarchical community modeling in a single framework to provide inferences on species-specific and community occurrence dynamics using multiple data sources. We use simulations to compare the ICOM to previously developed hierarchical community occupancy models and single species integrated distribution models. We then apply our model to assess the occurrence and biodiversity dynamics of foliage-gleaning birds in the White Mountain National Forest in the northeastern USA from 2010-2018 using three independent data sources. Simulations reveal that integrating multiple data sources in the ICOM increased precision and accuracy of species and community level inferences compared to single data source models, although benefits of integration were dependent on data source quality (e.g., amount of replication). Compared to single species models, the ICOM yielded more precise species-level estimates. Within our case study, the ICOM had the highest out-of-sample predictive performance compared to single species models and models that used only a subset of the three data sources. The ICOM offers an attractive approach to estimate species and biodiversity dynamics, which is additionally valuable to inform management objectives of both individual species and their broader communities.
Learning meaningful representations of data that can address challenges such as batch effect correction and counterfactual inference is a central problem in many domains including computational biology. Adopting a Conditional VAE framework, we show that marginal independence between the representation and a condition variable plays a key role in both of these challenges. We propose the Contrastive Mixture of Posteriors (CoMP) method that uses a novel misalignment penalty defined in terms of mixtures of the variational posteriors to enforce this independence in latent space. We show that CoMP has attractive theoretical properties compared to previous approaches, and we prove counterfactual identifiability of CoMP under additional assumptions. We demonstrate state-of-the-art performance on a set of challenging tasks including aligning human tumour samples with cancer cell-lines, predicting transcriptome-level perturbation responses, and batch correction on single-cell RNA sequencing data. We also find parallels to fair representation learning and demonstrate that CoMP is competitive on a common task in the field.
Identifying potential drug targets using metabolic modeling requires integrating multiple modeling methods and heterogenous biological datasets, which can be challenging without sophisticated tools. We developed COMO, a user-friendly pipeline that integrates multi-omics data processing, context-specific metabolic model development, simulations, drug databases, and disease data to aid drug discovery. COMO can be installed as a Docker image and includes intuitive instructions within a Jupyter Lab environment. It provides a comprehensive solution for multi-omics integration of bulk and single-cell RNA-seq, microarrays, and proteomics to develop context-specific metabolic models. Using public databases, open-source solutions for model construction, and a streamlined approach for predicting repurposable drugs, COMO empowers researchers to investigate low-cost alternatives and novel disease treatments. As a case study, we used the pipeline to construct metabolic models of B cells, which simulate and analyze them to predict 25 and 23 metabolic drug targets for rheumatoid arthritis and systemic lupus erythematosus, respectively. COMO can be used to construct models for any cell or tissue type and identify drugs for any human disease. The pipeline has the potential to improve the health of the global community cost-effectively by providing high-confidence targets to pursue in preclinical and clinical studies.
Ontology Alignment is an important research problem applied to various fields such as data integration, data transfer, data preparation, etc. State-of-the-art (SOTA) Ontology Alignment systems typically use naive domain-dependent approaches with handcrafted rules or domain-specific architectures, making them unscalable and inefficient. In this work, we propose VeeAlign, a Deep Learning based model that uses a novel dual-attention mechanism to compute the contextualized representation of a concept which, in turn, is used to discover alignments. By doing this, not only is our approach able to exploit both syntactic and semantic information encoded in ontologies, it is also, by design, flexible and scalable to different domains with minimal effort. We evaluate our model on four different datasets from different domains and languages, and establish its superiority through these results as well as detailed ablation studies. The code and datasets used are available at https://github.com/Remorax/VeeAlign.
Integration of data from multiple omics techniques is becoming increasingly important in biomedical research. Due to non-uniformity and technical limitations in omics platforms, such integrative analyses on multiple omics, which we refer to as views, involve learning from incomplete observations with various view-missing patterns. This is challenging because i) complex interactions within and across observed views need to be properly addressed for optimal predictive power and ii) observations with various view-missing patterns need to be flexibly integrated. To address such challenges, we propose a deep variational information bottleneck (IB) approach for incomplete multi-view observations. Our method applies the IB framework on marginal and joint representations of the observed views to focus on intra-view and inter-view interactions that are relevant for the target. Most importantly, by modeling the joint representations as a product of marginal representations, we can efficiently learn from observed views with various view-missing patterns. Experiments on real-world datasets show that our method consistently achieves gain from data integration and outperforms state-of-the-art benchmarks.
Behavioural symptoms and urinary tract infections (UTI) are among the most common problems faced by people with dementia. One of the key challenges in the management of these conditions is early detection and timely intervention in order to reduce distress and avoid unplanned hospital admissions. Using in-home sensing technologies and machine learning models for sensor data integration and analysis provides opportunities to detect and predict clinically significant events and changes in health status. We have developed an integrated platform to collect in-home sensor data and performed an observational study to apply machine learning models for agitation and UTI risk analysis. We collected a large dataset from 88 participants with a mean age of 82 and a standard deviation of 6.5 (47 females and 41 males) to evaluate a new deep learning model that utilises attention and rational mechanism. The proposed solution can process a large volume of data over a period of time and extract significant patterns in a time-series data (i.e. attention) and use the extracted features and patterns to train risk analysis models (i.e. rational). The proposed model can explain the predictions by indicating which time-steps and features are used in a long series of time-series data. The model provides a recall of 91\% and precision of 83\% in detecting the risk of agitation and UTIs. This model can be used for early detection of conditions such as UTIs and managing of neuropsychiatric symptoms such as agitation in association with initial treatment and early intervention approaches. In our study we have developed a set of clinical pathways for early interventions using the alerts generated by the proposed model and a clinical monitoring team has been set up to use the platform and respond to the alerts according to the created intervention plans.
Matching is a task at the heart of any data integration process, aimed at identifying correspondences among data elements. Matching problems were traditionally solved in a semi-automatic manner, with correspondences being generated by matching algorithms and outcomes subsequently validated by human experts. Human-in-the-loop data integration has been recently challenged by the introduction of big data and recent studies have analyzed obstacles to effective human matching and validation. In this work we characterize human matching experts, those humans whose proposed correspondences can mostly be trusted to be valid. We provide a novel framework for characterizing matching experts that, accompanied with a novel set of features, can be used to identify reliable and valuable human experts. We demonstrate the usefulness of our approach using an extensive empirical evaluation. In particular, we show that our approach can improve matching results by filtering out inexpert matchers.
Heterogeneous graph representation learning aims to learn low-dimensional vector representations of different types of entities and relations to empower downstream tasks. Existing methods either capture semantic relationships but indirectly leverage node/edge attributes in a complex way, or leverage node/edge attributes directly without taking semantic relationships into account. When involving multiple convolution operations, they also have poor scalability. To overcome these limitations, this paper proposes a flexible and efficient Graph information propagation Network (GripNet) framework. Specifically, we introduce a new supergraph data structure consisting of supervertices and superedges. A supervertex is a semantically-coherent subgraph. A superedge defines an information propagation path between two supervertices. GripNet learns new representations for the supervertex of interest by propagating information along the defined path using multiple layers. We construct multiple large-scale graphs and evaluate GripNet against competing methods to show its superiority in link prediction, node classification, and data integration.
High-throughput molecular profiling technologies have produced high-dimensional multi-omics data, enabling systematic understanding of living systems at the genome scale. Studying molecular interactions across different data types helps reveal signal transduction mechanisms across different classes of molecules. In this paper, we develop a novel Bayesian representation learning method that infers the relational interactions across multi-omics data types. Our method, Bayesian Relational Learning (BayReL) for multi-omics data integration, takes advantage of a priori known relationships among the same class of molecules, modeled as a graph at each corresponding view, to learn view-specific latent variables as well as a multi-partite graph that encodes the interactions across views. Our experiments on several real-world datasets demonstrate enhanced performance of BayReL in inferring meaningful interactions compared to existing baselines.
Thanks to the increasing availability of drug-drug interactions (DDI) datasets and large biomedical knowledge graphs (KGs), accurate detection of adverse DDI using machine learning models becomes possible. However, it remains largely an open problem how to effectively utilize large and noisy biomedical KG for DDI detection. Due to its sheer size and amount of noise in KGs, it is often less beneficial to directly integrate KGs with other smaller but higher quality data (e.g., experimental data). Most of the existing approaches ignore KGs altogether. Some try to directly integrate KGs with other data via graph neural networks with limited success. Furthermore, most previous works focus on binary DDI prediction whereas the multi-typed DDI pharmacological effect prediction is a more meaningful but harder task. To fill the gaps, we propose a new method SumGNN: knowledge summarization graph neural network, which is enabled by a subgraph extraction module that can efficiently anchor on relevant subgraphs from a KG, a self-attention based subgraph summarization scheme to generate a reasoning path within the subgraph, and a multi-channel knowledge and data integration module that utilizes massive external biomedical knowledge for significantly improved multi-typed DDI predictions. SumGNN outperforms the best baseline by up to 5.54\%, and the performance gain is particularly significant in low data relation types. In addition, SumGNN provides interpretable prediction via the generated reasoning paths for each prediction.
When using Markov chain Monte Carlo (MCMC) algorithms to perform inference for Bayesian clustering models, such as mixture models, the output is typically a sample of clusterings (partitions) drawn from the posterior distribution. In practice, a key challenge is how to summarise this output. Here we build upon the notion of the posterior similarity matrix (PSM) in order to suggest new approaches for summarising the output of MCMC algorithms for Bayesian clustering models. A key contribution of our work is the observation that PSMs are positive semi-definite, and hence can be used to define probabilistically-motivated kernel matrices that capture the clustering structure present in the data. This observation enables us to employ a range of kernel methods to obtain summary clusterings, and otherwise exploit the information summarised by PSMs. For example, if we have multiple PSMs, each corresponding to a different dataset on a common set of statistical units, we may use standard methods for combining kernels in order to perform integrative clustering. We may moreover embed PSMs within predictive kernel models in order to perform outcome-guided data integration. We demonstrate the performances of the proposed methods through a range of simulation studies as well as two real data applications. R code is available at https://github.com/acabassi/combine-psms.
While the biomedical community has published several "open data" sources in the last decade, most researchers still endure severe logistical and technical challenges to discover, query, and integrate heterogeneous data and knowledge from multiple sources. To tackle these challenges, the community has experimented with Semantic Web and linked data technologies to create the Life Sciences Linked Open Data (LSLOD) cloud. In this paper, we extract schemas from more than 80 publicly available biomedical linked data graphs into an LSLOD schema graph and conduct an empirical meta-analysis to evaluate the extent of semantic heterogeneity across the LSLOD cloud. We observe that several LSLOD sources exist as stand-alone data sources that are not inter-linked with other sources, use unpublished schemas with minimal reuse or mappings, and have elements that are not useful for data integration from a biomedical perspective. We envision that the LSLOD schema graph and the findings from this research will aid researchers who wish to query and integrate data and knowledge from multiple biomedical sources simultaneously on the Web.
Selectivity estimation aims at estimating the number of database objects that satisfy a selection criterion. Answering this problem accurately and efficiently is essential to many applications, such as density estimation, outlier detection, query optimization, and data integration. The estimation problem is especially challenging for large-scale high-dimensional data due to the curse of dimensionality, the large variance of selectivity across different queries, and the need to make the estimator consistent (i.e., the selectivity is non-decreasing in the threshold). We propose a new deep learning-based model that learns a query-dependent piecewise linear function as selectivity estimator, which is flexible to fit the selectivity curve of any distance function and query object, while guaranteeing that the output is non-decreasing in the threshold. To improve the accuracy for large datasets, we propose to partition the dataset into multiple disjoint subsets and build a local model on each of them. We perform experiments on real datasets and show that the proposed model consistently outperforms state-of-the-art models in accuracy in an efficient way and is useful for real applications.
Recent advances in biological research have seen the emergence of high-throughput technologies with numerous applications that allow the study of biological mechanisms at an unprecedented depth and scale. A large amount of genomic data is now distributed through consortia like The Cancer Genome Atlas (TCGA), where specific types of biological information on specific type of tissue or cell are available. In cancer research, the challenge is now to perform integrative analyses of high-dimensional multi-omic data with the goal to better understand genomic processes that correlate with cancer outcomes, e.g. elucidate gene networks that discriminate a specific cancer subgroups (cancer sub-typing) or discovering gene networks that overlap across different cancer types (pan-cancer studies). In this paper, we propose a novel mixed graphical model approach to analyze multi-omic data of different types (continuous, discrete and count) and perform model selection by extending the Birth-Death MCMC (BDMCMC) algorithm initially proposed by \citet{stephens2000bayesian} and later developed by \cite{mohammadi2015bayesian}. We compare the performance of our method to the LASSO method and the standard BDMCMC method using simulations and find that our method is superior in terms of both computational efficiency and the accuracy of the model selection results. Finally, an application to the TCGA breast cancer data shows that integrating genomic information at different levels (mutation and expression data) leads to better subtyping of breast cancers.