Analytics Lab

Background: In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. Findings: The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions: The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.

Asthmatic patients are currently classified as either severe or non-severe based primarily on their response to glucocorticoids. However, because this classification is based on a post-hoc assessment of treatment response, it does not inform the rational staging of disease or therapy. Recent studies in other diseases suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. We therefore measured cytokine values in bronchoalveolar lavage (BAL) samples of the lower respiratory tract obtained from 83 asthma patients, and used bipartite network visualizations with associated quantitative measures to conduct an exploratory analysis of the co-occurrence of cytokines across patients. The analysis helped to identify three clusters of patients which had a complex but understandable interaction with three clusters of cytokines, leading to insights for a state-based classification of asthma patients. Furthermore, while the patient clusters were significantly different based on key pulmonary functions, they appeared to have no significant relationship to the current classification of asthma patients. These results suggest the need to define a molecular-based classification of asthma patients, which could improve the diagnosis and treatment of this disease.

Although many cancer patients experience multiple concurrent symptoms, most studies have either focused on the analysis of single symptoms, or have used methods such as factor analysis that make a priori assumptions about how the data is structured. This article addresses both limitations by first visually exploring the data to identify patterns in the co-occurrence of multiple symptoms, and then using those insights to select and develop quantitative measures to analyze and validate the results.

In query learning, the goal is to identify an unknown object while minimizing the number of yes or no questions (queries) posed about that object. We consider three extensions of this fundamental problem that are motivated by practical considerations in real-world, time-critical identification tasks such as emergency response. First, we consider the problem where the objects are partitioned into groups, and the goal is to identify only the group to which the object belongs. Second, we address the situation where the queries are partitioned into groups, and an algorithm may suggest a group of queries to a human user, who then selects the actual query. Third, we consider the problem of query learning in the presence of persistent query noise, and relate it to group identification. To address these problems we show that a standard algorithm for query learning, known as the splitting algorithm or generalized binary search, may be viewed as a generalization of Shannon-Fano coding. We then extend this result to the group-based settings, leading to new algorithms. The performance of our algorithms is demonstrated on simulated data and on a database used by first responders for toxic chemical identification. 1 http://hazmap.nlm.nih.gov/ 1 arXiv:0911.4511v1 [stat.ML]

In applications such as active learning and disease/fault diagnosis, one often encounters the problem of identifying an unknown object through a minimal number of queries. This problem has been referred to as query learning or object/entity identification. We consider three extensions of this fundamental problem that are motivated by practical considerations in real-world,time-critical identification tasks such as emergency response. First, we consider the problem where the objects are partitioned into groups, and the goal is to identify only the group to which the object belongs. Second, we address the situation where the queries are partitioned into groups, and an algorithm may suggest a group of queries to a human user, who then selects the actual query. Third, we consider the problem of object identification in the presence of persistent query noise, and relate it to group identification. To address these problems we show that a standard algorithm for object identification, known as generalized binary search, may be viewed as a generalization of Shannon-Fano coding. We then extend this result to the group-based settings, leading to new algorithms, whose performance is demonstrated through a logarithmic approximation bound, and through experiments on simulated data and a database used for toxic chemical identification.

The problem of active diagnosis arises in several applications such as disease diagnosis and fault diagnosis in computer networks, where the goal is to rapidly identify the binary states of a set of objects (e.g., faulty or working) by sequentially selecting, and observing, potentially noisy responses to binary valued queries. Previous work in this area chooses queries sequentially based on Information gain, and the object states are inferred by maximum a posteriori (MAP) estimation. In this work, rather than MAP estimation, we aim to rank objects according to their posterior fault probability. We propose a greedy algorithm to choose queries sequentially by maximizing the area under the ROC curve associated with the ranked list. The proposed algorithm overcomes limitations of existing work. When multiple faults may be present, the proposed algorithm does not rely on belief propagation, making it feasible for large scale networks with little loss in performance. When a single fault is present, the proposed algorithm can be implemented without knowledge of the underlying query noise distribution, making it robust to any misspecification of these noise parameters. We demonstrate the performance of the proposed algorithm through experiments on computer networks, a toxic chemical database, and synthetic datasets.