This document provides the foundations behind the functionality provided by the @math G library (this https URL), focusing on the basic operations the library provides: subsumption, refinement of directed labeled graphs, and distance similarity assessment between directed labeled graphs. @math G development was initially supported by the National Science Foundation, by the EAGER grant IIS-1551338.
Similarity measures for specific application domains, such as molecular structures in domains of biology or chemistry have also been studied @cite_30 , and they are typically grouped into three classes @cite_43 : sequence similarities (e.g., for DNA fragments), fingerprint-based (transform each molecule into a sequence of binary features representing whether a particular molecule exhibits particular properties or contains certain substructures) and graph-based (based on maximum common sub-graphs). The latter is a computationally expensive process, and thus there are a number of strategies to simplify the computations (e.g., @cite_17 ).
@cite_30 @cite_43 @cite_17
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Generating novel graph structures that optimize given objectives while obeying some given underlying rules is fundamental for chemistry, biology and social science research. This is especially important in the task of molecular graph generation, whose goal is to discover novel molecules with desired properties such as drug-likeness and synthetic accessibility, while obeying physical laws such as chemical valency. However, designing models to find molecules that optimize desired properties while incorporating highly complex and non-differentiable rules remains to be a challenging task. Here we propose Graph Convolutional Policy Network (GCPN), a general graph convolutional network based model for goal-directed graph generation through reinforcement learning. The model is trained to optimize domain-specific rewards and adversarial loss through policy gradient, and acts in an environment that incorporates domain-specific rules. Experimental results show that GCPN can achieve 61 improvement on chemical property optimization over state-of-the-art baselines while resembling known molecules, and achieve 184 improvement on the constrained property optimization task. A citing sentence is one that appears in a scientific article and cites previous work. Citing sentences have been studied and used in many applications. For example, they have been used in scientific paper summarization, automatic survey generation, paraphrase identification, and citation function classification. Citing sentences that cite multiple papers are common in scientific writing. This observation should be taken into consideration when using citing sentences in applications. For instance, when a citing sentence is used in a summary of a scientific paper, only the fragments of the sentence that are relevant to the summarized paper should be included in the summary. In this paper, we present and compare three different approaches for identifying the fragments of a citing sentence that are related to a given target reference. Our methods are: word classification, sequence labeling, and segment classification. Our experiments show that segment classification achieves the best results. This paper reviews the use of similarity searching in chemical databases. It begins by introducing the concept of similarity searching, differentiating it from the more common substructure searching, and then discusses the current generation of fragment-based measures that are used for searching chemical structure databases. The next sections focus upon two of the principal characteristics of a similarity measure: the coefficient that is used to quantify the degree of structural resemblance between pairs of molecules and the structural representations that are used to characterize molecules that are being compared in a similarity calculation. New types of similarity measure are then compared with current approaches, and examples are given of several applications that are related to similarity searching. From bacteria following simple chemical gradients to the brain distinguishing complex odour information, the ability to recognize molecular patterns is essential for biological organisms. This type of information-processing function has been implemented using DNA-based neural networks, but has been limited to the recognition of a set of no more than four patterns, each composed of four distinct DNA molecules. Winner-take-all computation has been suggested as a potential strategy for enhancing the capability of DNA-based neural networks. Compared to the linear-threshold circuits and Hopfield networks used previously, winner-take-all circuits are computationally more powerful, allow simpler molecular implementation and are not constrained by the number of patterns and their complexity, so both a large number of simple patterns and a small number of complex patterns can be recognized. Here we report a systematic implementation of winner-take-all neural networks based on DNA-strand-displacement reactions. We use a previously developed seesaw DNA gate motif, extended to include a simple and robust component that facilitates the cooperative hybridization that is involved in the process of selecting a ‘winner’. We show that with this extended seesaw motif DNA-based neural networks can classify patterns into up to nine categories. Each of these patterns consists of 20 distinct DNA molecules chosen from the set of 100 that represents the 100 bits in 10 × 10 patterns, with the 20 DNA molecules selected tracing one of the handwritten digits ‘1’ to ‘9’. The network successfully classified test patterns with up to 30 of the 100 bits flipped relative to the digit patterns ‘remembered’ during training, suggesting that molecular circuits can robustly accomplish the sophisticated task of classifying highly complex and noisy information on the basis of similarity to a memory. We seek to automate the design of molecules based on specific chemical properties. In computational terms, this task involves continuous embedding and generation of molecular graphs. Our primary contribution is the direct realization of molecular graphs, a task previously approached by generating linear SMILES strings instead of graphs. Our junction tree variational autoencoder generates molecular graphs in two phases, by first generating a tree-structured scaffold over chemical substructures, and then combining them into a molecule with a graph message passing network. This approach allows us to incrementally expand molecules while maintaining chemical validity at every step. We evaluate our model on multiple tasks ranging from molecular generation to optimization. Across these tasks, our model outperforms previous state-of-the-art baselines by a significant margin. Preface Introduction Molecular Biology Mathematics, Statistics, and Computer Science Some Molecular Biology DNA and Proteins The Central Dogma The Genetic Code Transfer RNA and Protein Sequences Genes Are Not Simple Biological Chemistry Restriction Maps Introduction Graphs Interval Graphs Measuring Fragment Sizes Multiple Maps Double Digest Problem Classifying Multiple Solutions Algorithms for DDP Algorithms and Complexity DDP is N P-Complete Approaches to DDP Simulated Annealing: TSP and DDP Mapping with Real Data Cloning and Clone Libraries A Finite Number of Random Clones Libraries by Complete Digestion Libraries by Partial Digestion Genomes per Microgram Physical Genome Maps: Oceans, Islands, and Anchors Mapping by Fingerprinting Mapping by Anchoring An Overview of Clone Overlap Putting It Together Sequence Assembly Shotgun Sequencing Sequencing by Hybridization Shotgun Sequencing Revisited Databases and Rapid Sequence Analysis DNA and Protein Sequence Databases A Tree Representation of a Sequence Hashing a Sequence Repeats in a Sequence Sequence Comparison by Hashing Sequence Comparison with at most l Mismatches Sequence Comparison by Statistical Content Dynamic Programming Alignment of Two Sequences The Number of Alignments Shortest and Longest Paths in a Network Global Distance Alignment Global Similarity Alignment Fitting One Sequence into Another Local Alignment and Clumps Linear Space Algorithms Tracebacks Inversions Map Alignment Parametric Sequence Comparisons Multiple Sequence Alignment The Cystic Fibrosis Gene Dynamic Programming in r-Dimensions Weighted-Average Sequences Profile Analysis Alignment by Hidden Markov Models Consensus Word Analysis Probability and Statistics for Sequence Alignment Global Alignment Local Alignment Extreme Value Distributions The Chein-Stein Method Poisson Approximation and Long Matches Sequence Alignment with Scores Probability and Statistics for Sequence Patterns A Central Limit Theorem Nonoverlapping Pattern Counts Poisson Approximation Site Distributions RNA Secondary Structure Combinatorics Minimum Free-energy Structures Consensus folding Trees and Sequences Trees Distance Parsimony Maximum Likelihood Trees Sources and Perspectives Molecular Biology Physical Maps and Clone Libraries Sequence Assembly Sequence Comparisons Probability and Statistics RNA Secondary Structure Trees and Sequences References Problem Solutions and Hints Mathematical Notation Algorithm Index Author Index Subject Index Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. The tools of molecular biology were used to solve an instance of the directed Hamiltonian path problem. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This experiment demonstrates the feasibility of carrying out computations at the molecular level. The old Asian legend about the blind men and the elephant comes to mind when looking at how different authors of scientific papers describe a piece of related prior work. It turns out that different citations to the same paper often focus on different aspects of that paper and that neither provides a full description of its full set of contributions. In this article, we will describe our investigation of this phenomenon. We studied citation summaries in the context of research papers in the biomedical domain. A citation summary is the set of citing sentences for a given article and can be used as a surrogate for the actual article in a variety of scenarios. It contains information that was deemed by peers to be important. Our study shows that citation summaries overlap to some extent with the abstracts of the papers and that they also differ from them in that they focus on different aspects of these papers than do the abstracts. In addition to this, co-cited articles (which are pairs of articles cited by another article) tend to be similar. We show results based on a lexical similarity metric called cohesion to justify our claims. © 2008 Wiley Periodicals, Inc. Chemical reaction networks (CRNs) formally model chemistry in a well-mixed solution. CRNs are widely used to describe information processing occurring in natural cellular regulatory networks, and with upcoming advances in synthetic biology, CRNs are a promising language for the design of artificial molecular control circuitry. Nonetheless, despite the widespread use of CRNs in the natural sciences, the range of computational behaviors exhibited by CRNs is not well understood. CRNs have been shown to be efficiently Turing-universal (i.e., able to simulate arbitrary algorithms) when allowing for a small probability of error. CRNs that are guaranteed to converge on a correct answer, on the other hand, have been shown to decide only the semilinear predicates (a multi-dimensional generalization of "eventually periodic" sets). We introduce the notion of function, rather than predicate, computation by representing the output of a function @math f : N k ? N l by a count of some molecular species, i.e., if the CRN starts with @math x 1 , ? , x k molecules of some "input" species @math X 1 , ? , X k , the CRN is guaranteed to converge to having @math f ( x 1 , ? , x k ) molecules of the "output" species @math Y 1 , ? , Y l . We show that a function @math f : N k ? N l is deterministically computed by a CRN if and only if its graph @math ( x , y ) ? N k × N l | f ( x ) = y is a semilinear set. Finally, we show that each semilinear function f (a function whose graph is a semilinear set) can be computed by a CRN on input x in expected time @math O ( polylog ? x ? 1 ) . The molecule problem is that of determining the relative locations of a set of objects in Euclidean space relying only upon a sparse set of pairwise distance measurements. This NP-hard problem has applications in the determination of molecular conformation. The molecule problem can be naturally expressed as a continuous, global optimization problem, but it also has a rich combinatorial structure. This paper investigates how that structure can be exploited to simplify the optimization problem. In particular, we present a novel divide-and-conquer algorithm in which a large global optimization problem is replaced by a sequence of smaller ones. Since the cost of the optimization can grow exponentially with problem size, this approach holds the promise of a substantial improvement in performance. Our algorithmic development relies upon some recently published results in graph theory. We describe an implementation of this algorithm and report some results of its performance on a sample molecule. Measures of sequence similarity and distance based more or less explicitly on subword composition are attracting an increasing interest driven by intensive applications such as massive document classification and genome-wide molecular taxonomy. A uniform character of such measures is in some underlying notion of relative compressibility, whereby two similar sequences are expected to share a larger number of common substrings than two distant ones. This paper reviews some of the approaches to sequence comparison based on subword composition and suggests that their common denominator may ultimately reside in special classes of subwords, the nature of which resonates in interesting ways with the structure of popular subword trees and graphs. Here, we present MultiProt, a fully automated highly efficient technique to detect mul- tiple structural alignments of protein structures. MultiProt finds the common geometrical cores be- tween input molecules. To date, most methods for multiple alignment start from the pairwise align- ment solutions. This may lead to a small overall alignment. In contrast, our method derives multiple alignments from simultaneous superpositions of in- put molecules. Further, our method does not re- quire that all input molecules participate in the alignment. Actually, it efficiently detects high scor- ing partial multiple alignments for all possible num- ber of molecules in the input. To demonstrate the power of MultiProt, we provide a number of case studies. First, we demonstrate known multiple align- ments of protein structures to illustrate the perfor- mance of MultiProt. Next, we present various biologi- cal applications. These include: (1) a partial alignment of hinge-bent domains; (2) identification of functional groups of G-proteins; (3) analysis of binding sites; and (4) protein-protein interface align- ment. Some applications preserve the sequence or- der of the residues in the alignment, whereas others are order-independent. It is their residue sequence order-independence that allows application of MultiProt to derive multiple alignments of binding sites and of protein-protein interfaces, making Mul- tiProt an extremely useful structural tool. Proteins Power-law distributions have been observed in a wide variety of areas. To our knowledge however, there has been no systematic observation of power-law distributions in chemoinformatics. Here, we present several examples of power-law distributions arising from the features of small, organic molecules. The distributions of rigid segments and ring systems, the distributions of molecular paths and circular substructures, and the sizes of molecular similarity clusters all show linear trends on log-log rank frequency plots, suggesting underlying power-law distributions. The number of unique features also follow Heaps'-like laws. The characteristic exponents of the power-laws lie in the 1.5-3 range, consistently with the exponents observed in other power-law phenomena. The power-law nature of these distributions leads to several applications including the prediction of the growth of available data through Heaps' law and the optimal allocation of experimental or computational resources via the 80 20 rule. More importantly, we also show how the power-laws can be leveraged to efficiently compress chemical fingerprints in a lossless manner, useful for the improved storage and retrieval of molecules in large chemical databases. eep generative models for graph-structured data offer a new angle on the problem of chemical synthesis: by optimizing differentiable models that directly generate molecular graphs, it is pos-sible to side-step expensive search procedures in the discrete and vast space of chemical structures. We introduce MolGAN, an implicit, likelihood-free generative model for small molecular graphs that circumvents the need for expensive graph matching procedures or node ordering heuris-tics of previous likelihood-based methods. Our method adapts generative adversarial networks (GANs) to operate directly on graph-structured data. We combine our approach with a reinforce-ment learning objective to encourage the genera-tion of molecules with specific desired chemical properties. In experiments on the QM9 chemi-cal database, we demonstrate that our model is capable of generating close to 100 valid com-pounds. MolGAN compares favorably both to recent proposals that use string-based (SMILES) representations of molecules and to a likelihood-based method that directly generates graphs, al-beit being susceptible to mode collapse. The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes’ law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository. The ability to identify interesting and repetitive substructures is an essential component to discovering knowledge in structural data. We describe a new version of our SUBDUE substructure discovery system based on the minimum description length principle. The SUBDUE system discovers substructures that compress the original data and represent structural concepts in the data. By replacing previously-discovered substructures in the data, multiple passes of SUBDUE produce a hierarchical description of the structural regularities in the data. SUBDUE uses a computationally-bounded inexact graph match that identifies similar, but not identical, instances of a substructure and finds an approximate measure of closeness of two substructures when under computational constraints. In addition to the minimumdescription length principle, other background knowledge can be used by SUBDUE to guide the search towards more appropriate substructures. Experiments in a variety of domains demonstrate SUBDUE's ability to find substructures capable of compressing the original data and to discover structural concepts important to the domain. Patent prior art search is a type of search in the patent domain where documents are searched for that describe the work previously carried out related to a patent application. The goal of this search is to check whether the idea in the patent application is novel. Vocabulary mismatch is one of the main problems of patent retrieval which results in low retrievability of similar documents for a given patent application. In this paper we show how the term distribution of the cited documents in an initially retrieved ranked list can be used to address the vocabulary mismatch. We propose a method for query modeling estimation which utilizes the citation links in a pseudo relevance feedback set. We first build a topic dependent citation graph, starting from the initially retrieved set of feedback documents and utilizing citation links of feedback documents to expand the set. We identify the important documents in the topic dependent citation graph using a citation analysis measure. We then use the term distribution of the documents in the citation graph to estimate a query model by identifying the distinguishing terms and their respective weights. We then use these terms to expand our original query. We use CLEF-IP 2011 collection to evaluate the effectiveness of our query modeling approach for prior art search. We also study the influence of different parameters on the performance of the proposed method. The experimental results demonstrate that the proposed approach significantly improves the recall over a state-of-the-art baseline which uses the link-based structure of the citation graph but not the term distribution of the cited documents. We present a framework, which we call Molecule Deep @math -Networks (MolDQN), for molecule optimization by combining domain knowledge of chemistry and state-of-the-art reinforcement learning techniques (prioritized experience replay, double @math -learning, and randomized value functions). We directly define modifications on molecules, thereby ensuring 100 chemical validity. Further, we operate without pre-training on any dataset to avoid possible bias from the choice of that set. As a result, our model outperforms several other state-of-the-art algorithms by having a higher success rate of acquiring molecules with better properties. Inspired by problems faced during medicinal chemistry lead optimization, we extend our model with multi-objective reinforcement learning, which maximizes drug-likeness while maintaining similarity to the original molecule. We further show the path through chemical space to achieve optimization for a molecule to understand how the model works. Many real world graphs, such as the graphs of molecules, exhibit structure at multiple different scales, but most existing kernels between graphs are either purely local or purely global in character. In contrast, by building a hierarchy of nested subgraphs, the Multiscale Laplacian Graph kernels (MLG kernels) that we define in this paper can account for structure at a range of different scales. At the heart of the MLG construction is another new graph kernel, called the Feature Space Laplacian Graph kernel (FLG kernel), which has the property that it can lift a base kernel defined on the vertices of two graphs to a kernel between the graphs. The MLG kernel applies such FLG kernels to subgraphs recursively. To make the MLG kernel computationally feasible, we also introduce a randomized projection procedure, similar to the Nystr "om method, but for RKHS operators.