Efficient Node Proximity and Node Significance Computations in Graphs

abstract: Node proximity measures are commonly used for quantifying how nearby or otherwise related to two or more nodes in a graph are. Node significance measures are mainly used to find how much nodes are important in a graph. The measures of node proximity/significance have been highly effective in many predictions and applications. Despite their effectiveness, however, there are various shortcomings. One such shortcoming is a scalability problem due to their high computation costs on large size graphs and another problem on the measures is low accuracy when the significance of node and its degree in the graph are not related. The other problem is that their effectiveness is less when information for a graph is uncertain. For an uncertain graph, they require exponential computation costs to calculate ranking scores with considering all possible worlds. In this thesis, I first introduce Locality-sensitive, Re-use promoting, approximate Personalized PageRank (LR-PPR) which is an approximate personalized PageRank calculating node rankings for the locality information for seeds without calculating the entire graph and reusing the precomputed locality information for different locality combinations. For the identification of locality information, I present Impact Neighborhood Indexing (INI) to find impact neighborhoods with nodes' fingerprints propagation on the network. For the accuracy challenge, I introduce Degree Decoupled PageRank (D2PR) technique to improve the effectiveness of PageRank based knowledge discovery, especially considering the significance of neighbors and degree of a given node. To tackle the uncertain challenge, I introduce Uncertain Personalized PageRank (UPPR) to approximately compute personalized PageRank values on uncertainties of edge existence and Interval Personalized PageRank with Integration (IPPR-I) and Interval Personalized PageRank with Mean (IPPR-M) to compute ranking scores for the case when uncertainty exists on edge weights as interval values.Dissertation/ThesisDoctoral Dissertation Computer Science 201

VarSight: prioritizing clinically reported variants with binary classification algorithms.

BackgroundWhen applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient's phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.MethodsWe tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network.ResultsWe treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20.ConclusionsWe demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets

Probabilistic performance estimators for computational chemistry methods: Systematic Improvement Probability and Ranking Probability Matrix. I. Theory

The comparison of benchmark error sets is an essential tool for the evaluation of theories in computational chemistry. The standard ranking of methods by their Mean Unsigned Error is unsatisfactory for several reasons linked to the non-normality of the error distributions and the presence of underlying trends. Complementary statistics have recently been proposed to palliate such deficiencies, such as quantiles of the absolute errors distribution or the mean prediction uncertainty. We introduce here a new score, the systematic improvement probability (SIP), based on the direct system-wise comparison of absolute errors. Independently of the chosen scoring rule, the uncertainty of the statistics due to the incompleteness of the benchmark data sets is also generally overlooked. However, this uncertainty is essential to appreciate the robustness of rankings. In the present article, we develop two indicators based on robust statistics to address this problem: P_{inv}, the inversion probability between two values of a statistic, and \mathbf{P}_{r}, the ranking probability matrix. We demonstrate also the essential contribution of the correlations between error sets in these scores comparisons