Determining cellular lineage directed networks in hematopoiesis using single-cell transcriptomic data and volatility-constrained correlation.

Single-cell transcriptome sequencing (scRNA-seq) has revolutionized our understanding of cellular processes by enabling the analysis of expression profiles at an individual cell level. This technology has shown promise in uncovering new cell types, gene functions, cell differentiation, and trajectory inference through the study of various biological processes, such as hematopoiesis. Recent scRNA-seq analysis of mouse bone marrow cells has provided a network model of hematopoietic lineage. However, all data analyses have predicted undirected network maps for the associated cell trajectories. Moreover, the debate regarding the origin of basophil cells still persists. In this work, we apply the Volatility Constrained (VC) correlation method to predict not only the network structure but also the causality or directionality between the cell types present in the hematopoietic process. Our findings suggest a dual origin of basophils, from both granulocyte/macrophage and erythrocyte progenitors, the latter being a trajectory less explored in previous research. The proposed approach and predictions may assist in developing a complete hematopoietic process map, impacting our understanding of hematopoiesis and providing a robust directional network framework for further biomedical research.

Convolutional neural network approach to lung cancer classification integrating protein interaction network and gene expression profiles.

Deep learning technologies are permeating every field from image and speech recognition to computational and systems biology. However, the application of convolutional neural networks (CCNs) to "omics" data poses some difficulties, such as the processing of complex networks structures as well as its integration with transcriptome data. Here, we propose a CNN approach that combines spectral clustering information processing to classify lung cancer. The developed spectral-convolutional neural network based method achieves success in integrating protein interaction network data and gene expression profiles to classify lung cancer. The performed computational experiments suggest that in terms of accuracy the predictive performance of our proposed method was better than those of other machine learning methods such as SVM or Random Forest. Moreover, the computational results also indicate that the underlying protein network structure assists to enhance the predictions. Data and CNN code can be downloaded from the link: https://sites.google.com/site/nacherlab/analysis.

Identification of genes and critical control proteins associated with inflammatory breast cancer using network controllability.

One of the most aggressive forms of breast cancer is inflammatory breast cancer (IBC), whose lack of tumour mass also makes a prompt diagnosis difficult. Moreover, genomic differences between common breast cancers and IBC have not been completely assessed, thus substantially limiting the identification of biomarkers unique to IBC. Here, we developed a novel statistical analysis of gene expression profiles corresponding to microdissected IBC, non-IBC (nIBC) and normal samples that enabled us to identify a set of genes significantly associated with a specific disease state. Second, by using advanced methods based on controllability network theory, we identified a set of critical control proteins that uniquely and structurally control the entire proteome. By mapping high change variance genes in protein interaction networks, we found that a large statistically significant fraction of genes whose variance changed significantly between normal and IBC and nIBC disease states were among the set of critical control proteins. Moreover, this analysis identified the overlapping genes with the highest statistical significance; these genes may assist in developing future biomarkers and determining drug targets to disrupt the molecular pathways driving carcinogenesis in IBC.

Predicting link directionality in gene regulation from gene expression profiles using volatility-constrained correlation.

To uncover potential disease molecular pathways and signaling networks, we do not only need undirected maps but also we need to infer the directionality of functional or physical interactions between cellular components. A wide range of methods for identifying functional interactions between genes relies on correlations between experimental gene expression measurements to some extent. However, the standard Pearson or Spearman correlation-based approaches can only determine undirected correlations between cellular components. Here, we apply a volatility-constrained correlation method for gene expression profiles that offers a new metric to capture directionality of interactions between genes. To evaluate the predictions we used four datasets distributed by the DREAM5 network inference challenge including an in silico-constructed network and three organisms such as S. aureus, E. coli and S. cerevisiae. The predictions performed by our proposed method were compared to a gold standard of experimentally verified directionality of genetic regulatory links. Our findings show that our method successfully predicts the genetic interaction directionality with a success rate higher than 0.5 with high statistical significance.

Prospect theory for online financial trading.

Prospect theory is widely viewed as the best available descriptive model of how people evaluate risk in experimental settings. According to prospect theory, people are typically risk-averse with respect to gains and risk-seeking with respect to losses, known as the "reflection effect". People are much more sensitive to losses than to gains of the same magnitude, a phenomenon called "loss aversion". Despite of the fact that prospect theory has been well developed in behavioral economics at the theoretical level, there exist very few large-scale empirical studies and most of the previous studies have been undertaken with micro-panel data. Here we analyze over 28.5 million trades made by 81.3 thousand traders of an online financial trading community over 28 months, aiming to explore the large-scale empirical aspect of prospect theory. By analyzing and comparing the behavior of winning and losing trades and traders, we find clear evidence of the reflection effect and the loss aversion phenomenon, which are essential in prospect theory. This work hence demonstrates an unprecedented large-scale empirical evidence of prospect theory, which has immediate implication in financial trading, e.g., developing new trading strategies by minimizing the impact of the reflection effect and the loss aversion phenomenon. Moreover, we introduce three novel behavioral metrics to differentiate winning and losing traders based on their historical trading behavior. This offers us potential opportunities to augment online social trading where traders are allowed to watch and follow the trading activities of others, by predicting potential winners based on their historical trading behavior.

Foreign exchange market data analysis reveals statistical features that predict price movement acceleration.

Increasingly accessible financial data allow researchers to infer market-dynamics-based laws and to propose models that are able to reproduce them. In recent years, several stylized facts have been uncovered. Here we perform an extensive analysis of foreign exchange data that leads to the unveiling of a statistical financial law. First, our findings show that, on average, volatility increases more when the price exceeds the highest (or lowest) value, i.e., breaks the resistance line. We call this the breaking-acceleration effect. Second, our results show that the probability P(T) to break the resistance line in the past time T follows power law in both real data and theoretically simulated data. However, the probability calculated using real data is rather lower than the one obtained using a traditional Black-Scholes (BS) model. Taken together, the present analysis characterizes a different stylized fact of financial markets and shows that the market exceeds a past (historical) extreme price fewer times than expected by the BS model (the resistance effect). However, when the market does, we predict that the average volatility at that time point will be much higher. These findings indicate that any Markovian model does not faithfully capture the market dynamics.