A Comprehensive Analysis of the Structure-Function Relationship in Proteins Based on Local Structure Similarity

BACKGROUND:Sequence similarity to characterized proteins provides testable functional hypotheses for less than 50% of the proteins identified by genome sequencing projects. With structural genomics it is believed that structural similarities may give functional hypotheses for many of the remaining proteins. METHODOLOGY/PRINCIPAL FINDINGS:We provide a systematic analysis of the structure-function relationship in proteins using the novel concept of local descriptors of protein structure. A local descriptor is a small substructure of a protein which includes both short- and long-range interactions. We employ a library of commonly reoccurring local descriptors general enough to assemble most existing protein structures. We then model the relationship between these local shapes and Gene Ontology using rule-based learning. Our IF-THEN rule model offers legible, high resolution descriptions that combine local substructures and is able to discriminate functions even for functionally versatile folds such as the frequently occurring TIM barrel and Rossmann fold. By evaluating the predictive performance of the model, we provide a comprehensive quantification of the structure-function relationship based only on local structure similarity. Our findings are, among others, that conserved structure is a stronger prerequisite for enzymatic activity than for binding specificity, and that structure-based predictions complement sequence-based predictions. The model is capable of generating correct hypotheses, as confirmed by a literature study, even when no significant sequence similarity to characterized proteins exists. CONCLUSIONS/SIGNIFICANCE:Our approach offers a new and complete description and quantification of the structure-function relationship in proteins. By demonstrating how our predictions offer higher sensitivity than using global structure, and complement the use of sequence, we show that the presented ideas could advance the development of meta-servers in function prediction

Incremental Entity Resolution from Linked Documents

In many government applications we often find that information about entities, such as persons, are available in disparate data sources such as passports, driving licences, bank accounts, and income tax records. Similar scenarios are commonplace in large enterprises having multiple customer, supplier, or partner databases. Each data source maintains different aspects of an entity, and resolving entities based on these attributes is a well-studied problem. However, in many cases documents in one source reference those in others; e.g., a person may provide his driving-licence number while applying for a passport, or vice-versa. These links define relationships between documents of the same entity (as opposed to inter-entity relationships, which are also often used for resolution). In this paper we describe an algorithm to cluster documents that are highly likely to belong to the same entity by exploiting inter-document references in addition to attribute similarity. Our technique uses a combination of iterative graph-traversal, locality-sensitive hashing, iterative match-merge, and graph-clustering to discover unique entities based on a document corpus. A unique feature of our technique is that new sets of documents can be added incrementally while having to re-resolve only a small subset of a previously resolved entity-document collection. We present performance and quality results on two data-sets: a real-world database of companies and a large synthetically generated `population' database. We also demonstrate benefit of using inter-document references for clustering in the form of enhanced recall of documents for resolution.Comment: 15 pages, 8 figures, patented wor

MinoanER: Schema-Agnostic, Non-Iterative, Massively Parallel Resolution of Web Entities

Entity Resolution (ER) aims to identify different descriptions in various Knowledge Bases (KBs) that refer to the same entity. ER is challenged by the Variety, Volume and Veracity of entity descriptions published in the Web of Data. To address them, we propose the MinoanER framework that simultaneously fulfills full automation, support of highly heterogeneous entities, and massive parallelization of the ER process. MinoanER leverages a token-based similarity of entities to define a new metric that derives the similarity of neighboring entities from the most important relations, as they are indicated only by statistics. A composite blocking method is employed to capture different sources of matching evidence from the content, neighbors, or names of entities. The search space of candidate pairs for comparison is compactly abstracted by a novel disjunctive blocking graph and processed by a non-iterative, massively parallel matching algorithm that consists of four generic, schema-agnostic matching rules that are quite robust with respect to their internal configuration. We demonstrate that the effectiveness of MinoanER is comparable to existing ER tools over real KBs exhibiting low Variety, but it outperforms them significantly when matching KBs with high Variety.Comment: Presented at EDBT 2001

A Fuzzy Logic Programming Environment for Managing Similarity and Truth Degrees

FASILL (acronym of "Fuzzy Aggregators and Similarity Into a Logic Language") is a fuzzy logic programming language with implicit/explicit truth degree annotations, a great variety of connectives and unification by similarity. FASILL integrates and extends features coming from MALP (Multi-Adjoint Logic Programming, a fuzzy logic language with explicitly annotated rules) and Bousi~Prolog (which uses a weak unification algorithm and is well suited for flexible query answering). Hence, it properly manages similarity and truth degrees in a single framework combining the expressive benefits of both languages. This paper presents the main features and implementations details of FASILL. Along the paper we describe its syntax and operational semantics and we give clues of the implementation of the lattice module and the similarity module, two of the main building blocks of the new programming environment which enriches the FLOPER system developed in our research group.Comment: In Proceedings PROLE 2014, arXiv:1501.0169

ERBlox: Combining Matching Dependencies with Machine Learning for Entity Resolution

Entity resolution (ER), an important and common data cleaning problem, is about detecting data duplicate representations for the same external entities, and merging them into single representations. Relatively recently, declarative rules called "matching dependencies" (MDs) have been proposed for specifying similarity conditions under which attribute values in database records are merged. In this work we show the process and the benefits of integrating four components of ER: (a) Building a classifier for duplicate/non-duplicate record pairs built using machine learning (ML) techniques; (b) Use of MDs for supporting the blocking phase of ML; (c) Record merging on the basis of the classifier results; and (d) The use of the declarative language "LogiQL" -an extended form of Datalog supported by the "LogicBlox" platform- for all activities related to data processing, and the specification and enforcement of MDs.Comment: Final journal version, with some minor technical corrections. Extended version of arXiv:1508.0601

Neural Nearest Neighbors Networks

Non-local methods exploiting the self-similarity of natural signals have been well studied, for example in image analysis and restoration. Existing approaches, however, rely on k-nearest neighbors (KNN) matching in a fixed feature space. The main hurdle in optimizing this feature space w.r.t. application performance is the non-differentiability of the KNN selection rule. To overcome this, we propose a continuous deterministic relaxation of KNN selection that maintains differentiability w.r.t. pairwise distances, but retains the original KNN as the limit of a temperature parameter approaching zero. To exploit our relaxation, we propose the neural nearest neighbors block (N3 block), a novel non-local processing layer that leverages the principle of self-similarity and can be used as building block in modern neural network architectures. We show its effectiveness for the set reasoning task of correspondence classification as well as for image restoration, including image denoising and single image super-resolution, where we outperform strong convolutional neural network (CNN) baselines and recent non-local models that rely on KNN selection in hand-chosen features spaces.Comment: to appear at NIPS*2018, code available at https://github.com/visinf/n3net

Qualitative Effects of Knowledge Rules in Probabilistic Data Integration

One of the problems in data integration is data overlap: the fact that different data sources have data on the same real world entities. Much development time in data integration projects is devoted to entity resolution. Often advanced similarity measurement techniques are used to remove semantic duplicates from the integration result or solve other semantic conflicts, but it proofs impossible to get rid of all semantic problems in data integration. An often-used rule of thumb states that about 90% of the development effort is devoted to solving the remaining 10% hard cases. In an attempt to significantly decrease human effort at data integration time, we have proposed an approach that stores any remaining semantic uncertainty and conflicts in a probabilistic database enabling it to already be meaningfully used. The main development effort in our approach is devoted to defining and tuning knowledge rules and thresholds. Rules and thresholds directly impact the size and quality of the integration result. We measure integration quality indirectly by measuring the quality of answers to queries on the integrated data set in an information retrieval-like way. The main contribution of this report is an experimental investigation of the effects and sensitivity of rule definition and threshold tuning on the integration quality. This proves that our approach indeed reduces development effort — and not merely shifts the effort to rule definition and threshold tuning — by showing that setting rough safe thresholds and defining only a few rules suffices to produce a ‘good enough’ integration that can be meaningfully used