Going the distance for protein function prediction: a new distance metric for protein interaction networks

Due to an error introduced in the production process, the x-axes in the first panels of Figure 1 and Figure 7 are not formatted correctly. The correct Figure 1 can be viewed here: http://dx.doi.org/10.1371/annotation/343bf260-f6ff-48a2-93b2-3cc79af518a9In protein-protein interaction (PPI) networks, functional similarity is often inferred based on the function of directly interacting proteins, or more generally, some notion of interaction network proximity among proteins in a local neighborhood. Prior methods typically measure proximity as the shortest-path distance in the network, but this has only a limited ability to capture fine-grained neighborhood distinctions, because most proteins are close to each other, and there are many ties in proximity. We introduce diffusion state distance (DSD), a new metric based on a graph diffusion property, designed to capture finer-grained distinctions in proximity for transfer of functional annotation in PPI networks. We present a tool that, when input a PPI network, will output the DSD distances between every pair of proteins. We show that replacing the shortest-path metric by DSD improves the performance of classical function prediction methods across the board.MC, HZ, NMD and LJC were supported in part by National Institutes of Health (NIH) R01 grant GM080330. JP was supported in part by NIH grant R01 HD058880. This material is based upon work supported by the National Science Foundation under grant numbers CNS-0905565, CNS-1018266, CNS-1012910, and CNS-1117039, and supported by the Army Research Office under grant W911NF-11-1-0227 (to MEC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

Unconventional machine learning of genome-wide human cancer data

Recent advances in high-throughput genomic technologies coupled with exponential increases in computer processing and memory have allowed us to interrogate the complex aberrant molecular underpinnings of human disease from a genome-wide perspective. While the deluge of genomic information is expected to increase, a bottleneck in conventional high-performance computing is rapidly approaching. Inspired in part by recent advances in physical quantum processors, we evaluated several unconventional machine learning (ML) strategies on actual human tumor data. Here we show for the first time the efficacy of multiple annealing-based ML algorithms for classification of high-dimensional, multi-omics human cancer data from the Cancer Genome Atlas. To assess algorithm performance, we compared these classifiers to a variety of standard ML methods. Our results indicate the feasibility of using annealing-based ML to provide competitive classification of human cancer types and associated molecular subtypes and superior performance with smaller training datasets, thus providing compelling empirical evidence for the potential future application of unconventional computing architectures in the biomedical sciences

Integrative OMICS Data-Driven Procedure Using a Derivatized Meta-Analysis Approach

The wealth of high-throughput data has opened up new opportunities to analyze and describe biological processes at higher resolution, ultimately leading to a significant acceleration of scientific output using high-throughput data from the different omics layers and the generation of databases to store and report raw datasets. The great variability among the techniques and the heterogeneous methodologies used to produce this data have placed meta-analysis methods as one of the approaches of choice to correlate the resultant large-scale datasets from different research groups. Through multi-study meta-analyses, it is possible to generate results with greater statistical power compared to individual analyses. Gene signatures, biomarkers and pathways that provide new insights of a phenotype of interest have been identified by the analysis of large-scale datasets in several fields of science. However, despite all the efforts, a standardized regulation to report large-scale data and to identify the molecular targets and signaling networks is still lacking. Integrative analyses have also been introduced as complementation and augmentation for meta-analysis methodologies to generate novel hypotheses. Currently, there is no universal method established and the different methods available follow different purposes. Herein we describe a new unifying, scalable and straightforward methodology to meta-analyze different omics outputs, but also to integrate the significant outcomes into novel pathways describing biological processes of interest. The significance of using proper molecular identifiers is highlighted as well as the potential to further correlate molecules from different regulatory levels. To show the methodology's potential, a set of transcriptomic datasets are meta-analyzed as an example

Data fusion of complementary information from parietal and occipital event related potentials for early diagnosis of Alzheimer\u27s disease

The number of the elderly population affected by Alzheimer\u27s disease is rapidly rising. The need to find an accurate, inexpensive, and non-intrusive procedure that can be made available to community healthcare providers for the early diagnosis of Alzheimer\u27s disease is becoming an increasingly urgent public health concern. Several recent studies have looked at analyzing electroencephalogram signals through the use of many signal processing techniques. While their methods show great promise, the final outcome of these studies has been largely inconclusive. The inherent difficulty of the problem may be the cause of this outcome, but most likely it is due to the inefficient use of the available information, as many of these studies have used only a single EEG source for the analysis. In this contribution, data from the event related potentials of 19 available electrodes of the EEG are analyzed. These signals are decomposed into different frequency bands using multiresolution wavelet analysis. Two data fusion approaches are then investigated: i.) concatenating features before presenting them to a classification algorithm with the expectation of creating a more informative feature space, and ii.) generating multiple classifiers each trained with a different combination of features obtained from various stimuli, electrode, and frequency bands. The classifiers are then combined through the weighted majority vote, product and sum rule combination schemes. The results indicate that a correct diagnosis performance of over 80% can be obtained by combining data primarily from parietal and occipital lobe electrodes. The performance significantly exceeds that reported from community clinic physicians, despite their access to the outcomes of longitudinal monitoring of the patients

PROTEIN FUNCTION, DIVERISTY AND FUNCTIONAL INTERPLAY

Functional annotations of novel or unknown proteins is one of the central problems in post-genomics bioinformatics research. With the vast expansion of genomic and proteomic data and technologies over the last decade, development of automated function prediction (AFP) methods for large-scale identification of protein function has be-come imperative in many aspects. In this research, we address two important divergences from the “one protein – one function” concept on which all existing AFP methods are developed