The whole-brain functional connectivity (FC) pattern obtained from resting-state functional magnetic resonance imaging data are commonly applied to study neuropsychiatric conditions such as autism spectrum disorder (ASD) by using different machine learning models. Recent studies indicate that both hyper- and hypo- aberrant ASD-associated FCs were widely distributed throughout the entire brain rather than only in some specific brain regions. Deep neural networks (DNN) with multiple hidden layers have shown the ability to systematically extract lower-to-higher level information from high dimensional data across a series of neural hidden layers, significantly improving classification accuracy for such data. In this study, a DNN with a novel feature selection method (DNN-FS) is developed for the high dimensional whole-brain resting-state FC pattern classification of ASD patients versus typical development (TD) controls. The feature selection method is able to help the DNN generate low dimensional high-quality representations of the whole-brain FC patterns by selecting features with high discriminating power from multiple trained sparse auto-encoders. For the comparison, a DNN without the feature selection method (DNN-woFS) is developed, and both of them are tested with different architectures (i.e., with different numbers of hidden layers/nodes). Results show that the best classification accuracy of 86.36% is generated by the DNN-FS approach with 3 hidden layers and 150 hidden nodes (3/150). Remarkably, DNN-FS outperforms DNN-woFS for all architectures studied. The most significant accuracy improvement was 9.09% with the 3/150 architecture. The method also outperforms other feature selection methods, e.g., two sample t-test and elastic net. In addition to improving the classification accuracy, a Fisher’s score-based biomarker identification method based on the DNN is also developed, and used to identify 32 FCs related to ASD. These FCs come from or cross different pre-defined brain networks including the default-mode, cingulo-opercular, frontal-parietal and cerebellum. Thirteen of them are statically significant between ASD and TD groups (two sample t test p-value < 0.05) while nineteen of them are not. The relationship between the statically significant FCs and the corresponding ASD behavior symptoms is discussed based on the literature and clinician’s expert knowledge. Meanwhile, the potential reason of obtaining nineteen FCs which are not statistically

Rapid and accurate identification of new essential genes in under-studied microorganisms will significantly improve our understanding of how a cell works and the ability to re-engineer microorganisms. However, predicting essential genes across distantly related organisms remains a challenge. Here, we present a machine learning-based integrative approach that reliably transfers essential gene annotations between distantly related bacteria. We focused on four bacterial species that have well-characterized essential genes, and tested the transferability between three pairs among them. For each pair, we trained our classifier to learn traits associated with essential genes in one organism, and applied it to make predictions in the other. The predictions were then evaluated by examining the agreements with the known essential genes in the target organism. Ten-fold cross-validation in the same organism yielded AUC scores between 0.86 and 0.93. Cross-organism predictions yielded AUC scores between 0.69 and 0.89. The transferability is likely affected by growth conditions, quality of the training data set and the evolutionary distance. We are thus the first to report that gene essentiality can be reliably predicted using features trained and tested in a distantly related organism. Our approach proves more robust and portable than existing approaches, significantly extending our ability to predict essential genes beyond orthologs.

The concept of Big Data is popular in a variety of domains. The purpose of this review was to summarize the features, applications, analysis approaches, and challenges of Big Data in health care. Big Data in health care has its own features, such as heterogeneity, incompleteness, timeliness and longevity, privacy, and ownership. These features bring a series of challenges for data storage, mining, and sharing to promote health-related research. To deal with these challenges, analysis approaches focusing on Big Data in health care need to be developed and laws and regulations for making use of Big Data in health care need to be enacted. From a patient perspective, application of Big Data analysis could bring about improved treatment and lower costs. In addition to patients, government, hospitals, and research institutions could also benefit from the Big Data in health care. The concept of Big Data is popular in a variety of domains. The purpose of this review was to summarize the features, applications, analysis approaches, and challenges of Big Data in health care. Big Data in health care has its own features, such as heterogeneity, incompleteness, timeliness and longevity, privacy, and ownership. These features bring a series of challenges for data storage, mining, and sharing to promote health-related research. To deal with these challenges, analysis approaches focusing on Big Data in health care need to be developed and laws and regulations for making use of Big Data in health care need to be enacted. From a patient perspective, application of Big Data analysis could bring about improved treatment and lower costs. In addition to patients, government, hospitals, and research institutions could also benefit from the Big Data in health care.

Breast cancer stem cells (BCSCs) contribute to intra-tumoral heterogeneity and therapeutic resistance. However, the binary concept of universal BCSCs co-existing with bulk tumor cells is over-simplified. Through single-cell RNA-sequencing, we found that Neu, PyMT and BRCA1-null mammary tumors each corresponded to a spectrum of minimally overlapping cell differentiation states without a universal BCSC population. Instead, our analyses revealed that these tumors contained distinct lineage-specific tumor propagating cells (TPCs) and this is reflective of the self-sustaining capabilities of lineage-specific stem/progenitor cells in the mammary epithelial hierarchy. By understanding the respective tumor hierarchies, we were able to identify CD14 as a TPC marker in the Neu tumor. Additionally, single-cell breast cancer subtype stratification revealed the co-existence of multiple breast cancer subtypes within tumors. Collectively, our findings emphasize the need to account for lineage-specific TPCs and the hierarchical composition within breast tumors, as these heterogenous sub-populations can have differential therapeutic susceptibilities.