Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Multi-class protein fold classification using a new ensemble machine learning approach.

Protein structure classification represents an important process in understanding the associations between sequence and structure as well as possible functional and evolutionary relationships. Recent structural genomics initiatives and other high-throughput experiments have populated the biological databases at a rapid pace. The amount of structural data has made traditional methods such as manual inspection of the protein structure become impossible. Machine learning has been widely applied to bioinformatics and has gained a lot of success in this research area. This work proposes a novel ensemble machine learning method that improves the coverage of the classifiers under the multi-class imbalanced sample sets by integrating knowledge induced from different base classifiers, and we illustrate this idea in classifying multi-class SCOP protein fold data. We have compared our approach with PART and show that our method improves the sensitivity of the classifier in protein fold classification. Furthermore, we have extended this method to learning over multiple data types, preserving the independence of their corresponding data sources, and show that our new approach performs at least as well as the traditional technique over a single joined data source. These experimental results are encouraging, and can be applied to other bioinformatics problems similarly characterised by multi-class imbalanced data sets held in multiple data sources

Predicting Pancreatic Cancer Using Support Vector Machine

This report presents an approach to predict pancreatic cancer using Support Vector Machine Classification algorithm. The research objective of this project it to predict pancreatic cancer on just genomic, just clinical and combination of genomic and clinical data. We have used real genomic data having 22,763 samples and 154 features per sample. We have also created Synthetic Clinical data having 400 samples and 7 features per sample in order to predict accuracy of just clinical data. To validate the hypothesis, we have combined synthetic clinical data with subset of features from real genomic data. In our results, we observed that prediction accuracy, precision, recall with just genomic data is 80.77%, 20%, 4%. Prediction accuracy, precision, recall with just synthetic clinical data is 93.33%, 95%, 30%. While prediction accuracy, precision, recall for combination of real genomic and synthetic clinical data is 90.83%, 10%, 5%. The combination of real genomic and synthetic clinical data decreased the accuracy since the genomic data is weakly correlated. Thus we conclude that the combination of genomic and clinical data does not improve pancreatic cancer prediction accuracy. A dataset with more significant genomic features might help to predict pancreatic cancer more accurately

Analyzing Learned Molecular Representations for Property Prediction

Advancements in neural machinery have led to a wide range of algorithmic solutions for molecular property prediction. Two classes of models in particular have yielded promising results: neural networks applied to computed molecular fingerprints or expert-crafted descriptors, and graph convolutional neural networks that construct a learned molecular representation by operating on the graph structure of the molecule. However, recent literature has yet to clearly determine which of these two methods is superior when generalizing to new chemical space. Furthermore, prior research has rarely examined these new models in industry research settings in comparison to existing employed models. In this paper, we benchmark models extensively on 19 public and 16 proprietary industrial datasets spanning a wide variety of chemical endpoints. In addition, we introduce a graph convolutional model that consistently matches or outperforms models using fixed molecular descriptors as well as previous graph neural architectures on both public and proprietary datasets. Our empirical findings indicate that while approaches based on these representations have yet to reach the level of experimental reproducibility, our proposed model nevertheless offers significant improvements over models currently used in industrial workflows

Automatic categorization of diverse experimental information in the bioscience literature

Background: Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and the Saccharomyces Genome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such as C. elegans and D. melanogaster to identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance. Results: We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction. Conclusions: Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort

Spiking neurons with short-term synaptic plasticity form superior generative networks

Spiking networks that perform probabilistic inference have been proposed both as models of cortical computation and as candidates for solving problems in machine learning. However, the evidence for spike-based computation being in any way superior to non-spiking alternatives remains scarce. We propose that short-term plasticity can provide spiking networks with distinct computational advantages compared to their classical counterparts. In this work, we use networks of leaky integrate-and-fire neurons that are trained to perform both discriminative and generative tasks in their forward and backward information processing paths, respectively. During training, the energy landscape associated with their dynamics becomes highly diverse, with deep attractor basins separated by high barriers. Classical algorithms solve this problem by employing various tempering techniques, which are both computationally demanding and require global state updates. We demonstrate how similar results can be achieved in spiking networks endowed with local short-term synaptic plasticity. Additionally, we discuss how these networks can even outperform tempering-based approaches when the training data is imbalanced. We thereby show how biologically inspired, local, spike-triggered synaptic dynamics based simply on a limited pool of synaptic resources can allow spiking networks to outperform their non-spiking relatives.Comment: corrected typo in abstrac