Defining subtypes of complex diseases such as cancer and stratifying patient groups with the same disease but different subtypes for targeted treatments is important for personalized and precision medicine. Approaches that incorporate multi-omic data are more advantageous to those using only one data type for patient clustering and disease subtype discovery. However, it is challenging to integrate multi-omic data as they are heterogeneous and noisy. In this paper, we present Affinity Network Fusion (ANF) to integrate multi-omic data for patient clustering. ANF first constructs patient affinity networks for each omic data type, and then calculates a fused network for spectral clustering. We applied ANF to a processed harmonized cancer dataset downloaded from GDC data portal consisting of 2193 patients, and generated promising results on clustering patients into correct disease types. Moreover, we developed a semi-supervised model combining ANF and neural network for few-shot learning. In several cases, the model can achieve greater than 90 acccuracy on test set with training less than 1 of the data. This demonstrates the power of ANF in learning a good representation of patients, and shows the great potential of semi-supervised learning in cancer patient clustering.
As it is challenging to define a proper prior distribution and learn a good posterior distribution with limited data, many other approaches do not use probabilistic modeling. For example, Similarity Network Fusion (SNF) @cite_8 constructs patient similarity networks using different types of omic features, and fuses multiple patient similarity networks to achieve a consensus'' network that is then used for clustering patients into disease subtypes.
@cite_8
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Similarity network fusion (SNF) is an approach to integrate multiple data types on the basis of similarity between biological samples rather than individual measurements. The authors demonstrate SNF by constructing patient networks to identify disease subtypes with differential survival profiles. Objective Build probabilistic topic model representations of hospital admissions processes and compare the ability of such models to predict clinical order patterns as compared to preconstructed order sets. @PARASPLIT Materials and Methods The authors evaluated the first 24 hours of structured electronic health record data for > 10 K inpatients. Drawing an analogy between structured items (e.g., clinical orders) to words in a text document, the authors performed latent Dirichlet allocation probabilistic topic modeling. These topic models use initial clinical information to predict clinical orders for a separate validation set of > 4 K patients. The authors evaluated these topic model-based predictions vs existing human-authored order sets by area under the receiver operating characteristic curve, precision, and recall for subsequent clinical orders. @PARASPLIT Results Existing order sets predict clinical orders used within 24 hours with area under the receiver operating characteristic curve 0.81, precision 16 , and recall 35 . This can be improved to 0.90, 24 , and 47 ( P < 10−20) by using probabilistic topic models to summarize clinical data into up to 32 topics. Many of these latent topics yield natural clinical interpretations (e.g., “critical care,” “pneumonia,” “neurologic evaluation”). @PARASPLIT Discussion Existing order sets tend to provide nonspecific, process-oriented aid, with usability limitations impairing more precise, patient-focused support. Algorithmic summarization has the potential to breach this usability barrier by automatically inferring patient context, but with potential tradeoffs in interpretability. @PARASPLIT Conclusion Probabilistic topic modeling provides an automated approach to detect thematic trends in patient care and generate decision support content. A potential use case finds related clinical orders for decision support. Clustering cancer patients into subgroups and identifying cancer subtypes is an important task in cancer genomics. Clustering based on comprehensive multi-omic molecular profiling can often achieve better results than those using a single data type, since each omic data type may contain complementary information. However, it is challenging to integrate heterogeneous omic data directly. Based on one popular method – Similarity Network Fusion (SNF), we presented Affinity Network Fusion (ANF), an “upgrade” of SNF with several advantages. Similar to SNF, ANF treats each omic data type as one view of patients and learns a fused affinity matrix for clustering. We applied ANF to a harmonized TCGA dataset consisting of 2193 patients, and generated promising results on clustering patients into correct disease types. Our experimental results also demonstrated the power of feature selection and transformation combined with using ANF in patient clustering. Moreover, eigengap analysis suggests that the learned affinity matrices of four cancer types using our proposed framework may have successfully captured patient group structure and can be used for discovering unknown cancer subtypes. Many interesting domains in machine learning can be viewed as networks, with relationships (e.g., friendships) connecting items (e.g., individuals). The Active Exploration (AE) task is to identify all items in a network with a desired trait (i.e., positive labels) given only partial information about the network. The AE process iteratively queries for labels or network structure within a limited budget; thus, accurate predictions prior to making each query is critical to maximizing the number of positives gathered. However, the targeted AE query process produces partially observed networks that can create difficulties for predictive modeling. In particular, we demonstrate that these partial networks can exhibit extreme label correlation bias, which makes it difficult for conventional relational learning methods to accurately estimate relational parameters. To overcome this issue, we model the joint distribution of possible edges and labels to improve learning and inference. Our proposed method, Probabilistic Relational Expectation Maximization (PR-EM), is the first AE approach to accurately learn the complex dependencies between attributes, labels, and structure to improve predictions. PR-EM utilizes collective inference over the missing relationships in the partial network to jointly infer unknown item traits. Further, we develop a linear inference algorithm to facilitate efficient use of PR-EM in large networks. We test our approach on four real world networks, showing that AE with PR-EM gathers significantly more positive items compared to state-of-the-art methods.