Multiple Instance Learning Problem Research Articles

A Novel Learning Formulation in a unified Min-Max Framework for Computer Aided Diagnosis

The computer aided diagnosis (CAD) problems of detecting potentially diseased structures from medical images are typically distinguished by the following challenging characteristics: extremely unbalanced data between negative and positive classes; stringent real-time requirement of on- line execution; multiple positive candidates generated for the same malignant structure that are highly correlated and spatially close to each other. To address all these problems, we propose a novel learning formulation to combine cascade classification and multiple instance learning (MIL) in a unified min-max framework, leading to a joint optimization problem which can be converted to a tractable quadratic ally constrained quadratic program and efficiently solved by block-coordinate optimization algorithms. We apply the proposed approach to the CAD problems of detecting pulmonary embolism and colon cancer from computed tomography images. Experimental results show that our approach significantly reduces the computational cost while yielding comparable detection accuracy to the current state-of-the-art MIL or cascaded classifiers. Although not specifically designed for balanced MIL problems, the pro- posed method achieves superior performance on balanced MIL benchmark data such as MUSK and image data sets

MIL-SKDE: Multiple-instance learning with supervised kernel density estimation

Multiple-instance learning (MIL) is a variation on supervised learning. Instead of receiving a set of labeled instances, the learner receives a set of bags that are labeled. Each bag contains many instances. The aim of MIL is to classify new bags or instances. In this work, we propose a novel algorithm, MIL-SKDE (multiple-instance learning with supervised kernel density estimation), which addresses MIL problem through an extended framework of “KDE (kernel density estimation)+mean shift”. Since the KDE+mean shift framework is an unsupervised learning method, we extend KDE to its supervised version, called supervised KDE (SKDE), by considering class labels of samples. To seek the modes (local maxima) of SKDE, we also extend mean shift to a supervised version by taking into account sample labels. SKDE is an alternative of the well-known diverse density estimation (DDE) whose modes are called concepts. Comparing to DDE, SKDE is more convenient to learn multi-modal concepts and robust to labeling noise (mistakenly labeled bags). Finally, each bag is mapped into a concept space where the multi-class SVM classifiers are learned. Experimental results demonstrate that our approach outperforms the state-of-the-art MIL approaches.

Seeing Is Believing: Video Classification for Computed Tomographic Colonography Using Multiple-Instance Learning

In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods.

Predicting MHC Class II Epitopes Using Separated Constructive Clustering Ensemble

Successful Prediction for MHC Class II epitopes is an essential step in designing Genetic Vaccines(1). MHC Class II epitopes are short peptides with length between 9 and 25 amino acids which are bound by MHC. These epitopes are recognized by T-Cell Receptors and leads to activation of cellular and humoral immune system and, ultimately, to ef- fective destruction of pathogenic organism. Successful prediction of MHC class II epitopes is more difficult than MHC class I epitopes due to open binding groove at both ends in class II molecules, this structure leads to variable length for MHC II epitopes and complicating the task for detecting the core binding 9-mer. Large efforts have been exerted in devel- oping algorithms to predict which peptides will bind to a given MHC class II molecules. In this paper we presented a novel classification algorithm for predicting MHC Class II epitopes using Multiple Instance Learning technique. Separated Con- structive Clustering Ensemble (SCCE) is our new version for Constructive Clustering Ensemble (CCE)(27). This method was used for converting multiple instance learning problem into normal Single Instance Problem. Most of the processing in this method lies mainly in vector preparation step before using classifier; Support Vector Machine (SVM) has been used as a method with proven performance in a wide range of practical applications(38). SCCE integrated many algorithms like Genetic Algorithm, K medoid clustering, Ensemble learning and Support vector machine in an orchestration to predict the MHC II epitopes. SCCE was tested over three benchmark data sets and proved to be very competitive with the state of art regression methods. SCCE achieved these results using only binder and non binder flags; without need for regression data. An implementation of MHCII-SCCE as an online web server for predicting MHC-II Epitopes is freely accessible at http://www.fci.cu.edu.eg:8080/MHCII_Server/MHCII SCCE Server 1.0.htm.

Predicting MHC-II Binding Affinity Using Multiple Instance Regression

Reliably predicting the ability of antigen peptides to bind to major histocompatibility complex class II (MHC-II) molecules is an essential step in developing new vaccines. Uncovering the amino acid sequence correlates of the binding affinity of MHC-II binding peptides is important for understanding pathogenesis and immune response. The task of predicting MHC-II binding peptides is complicated by the significant variability in their length. Most existing computational methods for predicting MHC-II binding peptides focus on identifying a nine amino acids core region in each binding peptide. We formulate the problems of qualitatively and quantitatively predicting flexible length MHC-II peptides as multiple instance learning and multiple instance regression problems, respectively. Based on this formulation, we introduce MHCMIR, a novel method for predicting MHC-II binding affinity using multiple instance regression. We present results of experiments using several benchmark data sets that show that MHCMIR is competitive with the state-of-the-art methods for predicting MHC-II binding peptides. An online web server that implements the MHCMIR method for MHC-II binding affinity prediction is freely accessible at http://ailab.cs.iastate.edu/mhcmir.

Maximum Margin Multiple Instance Clustering With Applications to Image and Text Clustering

In multiple instance learning problems, patterns are often given as bags and each bag consists of some instances. Most of existing research in the area focuses on multiple instance classification and multiple instance regression, while very limited work has been conducted for multiple instance clustering (MIC). This paper formulates a novel framework, maximum margin multiple instance clustering (M(3)IC), for MIC. However, it is impractical to directly solve the optimization problem of M(3)IC. Therefore, M(3)IC is relaxed in this paper to enable an efficient optimization solution with a combination of the constrained concave-convex procedure and the cutting plane method. Furthermore, this paper presents some important properties of the proposed method and discusses the relationship between the proposed method and some other related ones. An extensive set of empirical results are shown to demonstrate the advantages of the proposed method against existing research for both effectiveness and efficiency.

Random set framework for multiple instance learning

Multiple instance learning (MIL) is a technique used for learning a target concept in the presence of noise or in a condition of uncertainty. While standard learning techniques present the learner with individual samples, MIL alternatively presents the learner with sets of samples. Although sets are the primary elements used for analysis in MIL, research in this area has focused on using standard analysis techniques. In the following, a random set framework for multiple instance learning (RSF-MIL) is proposed that can directly perform analysis on sets. The proposed method uses random sets and fuzzy measures to model the MIL problem, thus providing a more natural mathematical framework, a more general MIL solution, and a more versatile learning tool. Comparative experimental results using RSF-MIL are presented for benchmark data sets. RSF-MIL is further compared to the state-of-the-art in landmine detection using ground penetrating radar data.

MILD: Multiple-Instance Learning via Disambiguation

In multiple-instance learning (MIL), an individual example is called an instance and a bag contains a single or multiple instances. The class labels available in the training set are associated with bags rather than instances. A bag is labeled positive if at least one of its instances is positive; otherwise, the bag is labeled negative. Since a positive bag may contain some negative instances in addition to one or more positive instances, the true labels for the instances in a positive bag may or may not be the same as the corresponding bag label and, consequently, the instance labels are inherently ambiguous. In this paper, we propose a very efficient and robust MIL method, called Multiple-Instance Learning via Disambiguation (MILD), for general MIL problems. First, we propose a novel disambiguation method to identify the true positive instances in the positive bags. Second, we propose two feature representation schemes, one for instance-level classification and the other for bag-level classification, to convert the MIL problem into a standard single-instance learning (SIL) problem that can be solved by well-known SIL algorithms, such as support vector machine. Third, an inductive semi-supervised learning method is proposed for MIL. We evaluate our methods extensively on several challenging MIL applications to demonstrate their promising efficiency, robustness, and accuracy.

An automatic feature generation approach to multiple instance learning and its applications to image databases

Automatic content-based image categorization is a challenging research topic and has many practical applications. Images are usually represented as bags of feature vectors, and the categorization problem is studied in the Multiple-Instance Learning (MIL) framework. In this paper, we propose a novel learning technique which transforms the MIL problem into a standard supervised learning problem by defining a feature vector for each image bag. Specifically, the feature vectors of the image bags are grouped into clusters and each cluster is given a label. Using these labels, each instance of an image bag can be replaced by a corresponding label to obtain a bag of cluster labels. Data mining can then be employed to uncover common label patterns for each image category. These label patterns are converted into bags of feature vectors; and they are used to transform each image bag in the data set into a feature vector such that each vector element is the distance of the image bag to a distinct pattern bag. With this new image representation, standard supervised learning algorithms can be applied to classify the images into the pre-defined categories. Our experimental results demonstrate the superiority of the proposed technique in categorization accuracy as compared to state-of-the-art methods.

Multiple instance learning via margin maximization

In this paper, we consider the classification problem within the multiple instance learning (MIL) context. Training data is composed of labeled bags of instances. Despite the large number of margin maximization based classification methods, there are only a few methods that consider the margin for MIL problems in the literature. We first formulate a combinatorial margin maximization problem for multiple instance classification and prove that it is NP -hard. We present a way to apply the kernel trick in this formulation for classifying nonlinear multiple instance data. We also propose a branch and bound algorithm and present computational results on publicly available benchmark data sets. Our approach outperforms a leading commercial solver in terms of the best integer solution and optimality gap in the majority of image annotation and molecular activity prediction test cases.

Multiple-Instance Learning Algorithms for Computer-Aided Detection

Many computer-aided diagnosis (CAD) problems can be best modelled as a multiple-instance learning (MIL) problem with unbalanced data, i.e., the training data typically consists of a few positive bags, and a very large number of negative instances. Existing MIL algorithms are much too computationally expensive for these datasets. We describe CH, a framework for learning a Convex Hull representation of multiple instances that is significantly faster than existing MIL algorithms. Our CH framework applies to any standard hyperplane-based learning algorithm, and for some algorithms, is guaranteed to find the global optimal solution. Experimental studies on two different CAD applications further demonstrate that the proposed algorithm significantly improves diagnostic accuracy when compared to both MIL and traditional classifiers. Although not designed for standard MIL problems (which have both positive and negative bags and relatively balanced datasets), comparisons against other MIL methods on benchmark problems also indicate that the proposed method is competitive with the state-of-the-art.

MILES: Multiple-Instance Learning via Embedded Instance Selection

Multiple-instance problems arise from the situations where training class labels are attached to sets of samples (named bags), instead of individual samples within each bag (called instances). Most previous multiple-instance learning (MIL) algorithms are developed based on the assumption that a bag is positive if and only if at least one of its instances is positive. Although the assumption works well in a drug activity prediction problem, it is rather restrictive for other applications, especially those in the computer vision area. We propose a learning method, MILES (Multiple-Instance Learning via Embedded instance Selection), which converts the multiple-instance learning problem to a standard supervised learning problem that does not impose the assumption relating instance labels to bag labels. MILES maps each bag into a feature space defined by the instances in the training bags via an instance similarity measure. This feature mapping often provides a large number of redundant or irrelevant features. Hence, 1-norm SVM is applied to select important features as well as construct classifiers simultaneously. We have performed extensive experiments. In comparison with other methods, MILES demonstrates competitive classification accuracy, high computation efficiency, and robustness to labeling uncertainty.

Image Categorization by Learning and Reasoning with Regions

Designing computer programs to automatically categorize images using low-level features is a challenging research topic in computer vision. In this paper, we present a new learning technique, which extends Multiple-Instance Learning (MIL), and its application to the problem of region-based image categorization. Images are viewed as bags, each of which contains a number of instances corresponding to regions obtained from image segmentation. The standard MIL problem assumes that a bag is labeled positive if at least one of its instances is positive; otherwise, the bag is negative. In the proposed MIL framework, DD-SVM, a bag label is determined by some number of instances satisfying various properties. DD-SVM first learns a collection of instance prototypes according to a Diverse Density (DD) function. Each instance prototype represents a class of instances that is more likely to appear in bags with the specific label than in the other bags. A nonlinear mapping is then defined using the instance prototypes and maps every bag to a point in a new feature space, named the bag feature space. Finally, standard support vector machines are trained in the bag feature space. We provide experimental results on an image categorization problem and a drug activity prediction problem.