Genome-Wide Protein Function Prediction through Multi-Instance Multi-Label Learning

Nature often brings several domains together to form multidomain and multifunctional proteins with a vast number of possibilities. In our previous study, we disclosed that the protein function prediction problem is naturally and inherently Multi-Instance Multilabel (MIML) learning tasks. Automated protein function prediction is typically implemented under the assumption that the functions of labeled proteins are complete; that is, there are no missing labels. In contrast, in practice just a subset of the functions of a protein are known, and whether this protein has other functions is unknown. It is evident that protein function prediction tasks suffer from weak-label problem; thus protein function prediction with incomplete annotation matches well with the MIML with weak-label learning framework. In this paper, we have applied the state-of-the-art MIML with weak-label learning algorithm MIMLwel for predicting protein functions in two typical real-world electricigens organisms which have been widely used in microbial fuel cells (MFCs) researches. Our experimental results validate the effectiveness of MIMLwel algorithm in predicting protein functions with incomplete annotation.

With the advances in genetic sequencing technology, the automated assignment of protein function has become a key challenge in bioinformatics and computational biology. In nature, many kinds of proteins consist of a variety of structural domains, and each domain almost holds its own function independently or implements a new function in cooperation with neighbors. Thus, a multi-domain protein function prediction problem can be converted into multi-instance multi-label (MIML) learning tasks. In this paper, we propose a novel ensemble MIML algorithm called multi-instance multi-label randomized clustering forest (MIMLRC-Forest) for protein function prediction. In MIMLRC-Forest, we develop a set of hierarchical clustering trees and conduct a label transfer mechanism to identify the relevant function labels in learning process. The clustering tree with a hierarchical structure can handle the multi-label problem by exploiting more discriminable label concepts at higher-level nodes and by transferring less discriminable labels into the lower-level nodes. Then, the label dependency can be computed by aggregating tree labels for protein function prediction. Extensive experiments on five real-world protein data sets show the effectiveness of the proposed algorithm compared with several state-of-the-art baselines, including MIMLSVM, MIMLNN, MIML-kNN, EnMIMLNN, and M3MIML.

Existing studies for automatic waveform recognition of overlapping signals have mostly been conducted in a supervised manner. Although demonstrating superior performance in recent years, supervised methods rely heavily on sufficient labeled samples, rely but the acquisition of annotated data is expensive, time-consuming, and sometimes rely infeasible. This shortage drives the need for semi-supervised learning methods, where the unlabeled samples can be fully exploited in the training stage. In addition, multi-instance multi-label (MIML) learning is essentially another weakly supervised learning protocol, and precisely fits the form of the time-frequency images TFIs obtained from the transformation of overlapping signals. In this paper, delving into the MIML learning problem, we leverage the advantage of adversarial training to formulate an effective algorithm MIML-GAN, which is tailored to the MIML problem of overlapping signal waveform recognition. After feeding the TFIs into the network, MIML-GAN approximates the distribution of the training data using the adversarial learning principle. Subsequently, the baglevel prediction can be derived from the instance-level prediction upon the MIML discriminator through adaptive threshold calibration. Specifically, we elaborately studied the global optimality of the MIML-GAN objective function, and extensive simulations are carried out with overlapping signal dataset, validating the ascendancy of the proposed method. Comparative experiments demonstrate that the proposed algorithm possesses promising feature representation capability, and outperforms the existing semi-supervised and supervised signal waveform recognition approaches.

Automated assignment of protein function has received considerable attention in recent years for genome-wide study. With the rapid accumulation of genome sequencing data produced by high-throughput experimental techniques, the process of manually predicting functional properties of proteins has become increasingly cumbersome. Such large genomics data sets can only be annotated computationally. However, automated assignment of functions to unknown protein is challenging due to its inherent difficulty and complexity. Previous studies have revealed that solving problems involving complicated objects with multiple semantic meanings using the multi-instance multi-label (MIML) framework is effective. For the protein function prediction problems, each protein object in nature may associate with distinct structural units (instances) and multiple functional properties (class labels) where each unit is described by an instance and each functional property is considered as a class label. Thus, it is convenient and natural to tackle the protein function prediction problem by using the MIML framework. In this paper, we propose a sparse Markov chain-based semi-supervised MIML method, called Sparse-Markov. A sparse transductive probability graph is constructed to encode the affinity information of the data based on ensemble of Hausdorff distance metrics. Our goal is to exploit the affinity between protein objects in the sparse transductive probability graph to seek a sparse steady state probability of the Markov chain model to do protein function prediction, such that two proteins are given similar functional labels if they are close to each other in terms of an ensemble Hausdorff distance in the graph. Experimental results on seven real-world organism data sets covering three biological domains show that our proposed Sparse-Markov method is able to achieve better performance than four state-of-the-art MIML learning algorithms.

In this paper, we seek to solve the problem of remote sensing image classification using Multi Instance Multi Label Learning (MIML) framework, where each image contain multiple regions (instances) corresponds to multiple objects (labels). MIML framework is more efficient than traditional learning framework for complicated objects such as satellite images. Existing MIML algorithms such as MIMLboost, MIMLsvm and MIMLfast have been found useful in scene classification and can provide multiple labels for each instance in complicated objects. The proposed approach was performed in two steps: In the first step, we process the dataset using segmentation and feature extraction. Images are ambiguous because they contain numerous objects so we consider that each image is a bag and various blocks in the image are instances. In the second step, we apply MIML to classify each block of images. According to the experimental results, the proposed method outperforms the state-of-the-art methods.

A fast Markov chain based algorithm for MIML learning

In this paper, we propose the MIML (Multi- Instance Multi-Label learning) framework which is associated with multiple class labels for Image Annotation. Compared to traditional learning frameworks, the MIML framework is more convenient and natural for representing complicated objects which have multiple semantic meanings. To learn from MIML examples we have taken a survey on MIML Boost, MIMLSVM, D-MIMLSVM, InsDif and SubCod algorithms. MIML Boost and MIML SVM are based on a simple degeneration strategy. Experiments based on this algorithm shows that solving problems involving complicated objects with multiple semantic meanings in the MIML framework can lead to good performance. As the degeneration process may lose information, we have considered D-MimlSvm algorithm which tackles MIML problems directly in a regularization framework. InsDif and SubCod algorithms works by transforming single-instances into the MIML representation for learning, while SubCod works by transforming single-label examples into the MIML representation for learning. We have compared the results of all the algorithms and have identified that InsDif framework leads to good performance rates.

In many real world applications, the concerned objects are with multiple labels, and can be represented as a bag of instances. Multi-instance Multi-label (MIML) learning provides a framework for handling such task and has exhibited excellent performance in various domains. In a MIML setting, the feature representation of instances usually has big impact on the final performance; inspired by the recent deep learning studies, in this paper, we propose the DeepMIML network which exploits deep neural network formation to generate instance representation for MIML. The sub-concept learning component of the DeepMIML structure reserves the instance-label relation discovery ability of MIML algorithms; that is, it can automatically locating the key input patterns that trigger the labels. The effectiveness of DeepMIML network is validated by experiments on various domains of data.

Image annotation plays a vital role in dealing with effective organization and retrieval of a large number of digital images. Multi-instance multi-label (MIML) learning can deal with complicated objects by solving the ambiguity in both input and output space. Image bag generator is a key component of MIML algorithms. A bag generator takes an image as its input and generates a set of instances for that image. These instances are the various subparts of the original image and collectively describe the image in totality. This paper proposes two new bag generators which can generate an instance for every possible object present in the image. The proposed bag generators effectively utilize the correlations among pixels to generate instances. We demonstrate that the proposed bag generators outperform the state-of-the-art bag generator methods.

Multilabel learning (MLL), as a hot topic in the field of machine learning, has attracted wide attention from many scholars due to its ability to express output space polysemy. In recent years, a large number of achievements about MLL have emerged. Among these achievements, there are several typical issues worthy of attention. Firstly, the correlation among labels plays a key role in improving MLL model training process. Many MLL algorithms try to fully and effectively use the correlation among labels to improve the performance. Secondly, existing MLL evaluation metrics, which is different from those in binary classification, often reflects the generalization performance of MLL classifiers in some aspects. How to choose metrics in algorithms to improve their generalization performance and fairness is another issue that should be concerned. Thirdly, in many practical MLL applications, there are many unlabeled instances due to their labeling cost in training datasets. How to use the wealth information contained in the correlation among unlabeled instances may contribute to reducing of the labeling cost in MLL and improving performance. Fourthly, labels assigned to instances may not be equally descriptive in many applications. How to describe the importance of each label in output space to an instance has become one of research points that many scholars have paid attention to in recent years. This paper reviews the MLL-related research results of correlation among labels, evaluation metric, multilabel semisupervised learning, and label distribution learning (LDL) from a theoretical and algorithmic perspective. Finally, the related research work on MLL is summarized and discussed.

Multi instance multi label learning is a framework in which objects are represented as bags of instances and labels are provided at the bag level. Instance annotation is the problem of assigning labels to the instances in a bag given only the bag label. Recently, OR-ed logistic regression (OR-LR) model and an EM based inference method have been proposed for instance annotation. Due to the linear nature of the logistic regression function, OR-LR performance on linearly inseparable data is limited. This paper addresses this problem by proposing a regularized kernel-based extension to the OR-LR framework. Experiments show that the kernel-based OR-LR algorithm achieves a significant improvement in classification accuracy over the linear OR-LR from 3% to 9% on audio bird song and image annotation datasets and two synthetic datasets.

Multi-label learning draws great interests in many real world applications. It is a highly costly task to assign many labels by the oracle for one instance. Meanwhile, it is also hard to build a good model without diagnosing discriminative labels. Can we reduce the label costs and improve the ability to train a good model for multi-label learning simultaneously? Active learning addresses the less training samples problem by querying the most valuable samples to achieve a better performance with little costs. In multi-label active learning, some researches have been done for querying the relevant labels with less training samples or querying all labels without diagnosing the discriminative information. They all cannot effectively handle the outlier labels for the measurement of uncertainty. Since maximum correntropy criterion (MCC) provides a robust analysis for outliers in many machine learning and data mining algorithms, in this paper, we derive a robust multi-label active learning algorithm based on an MCC by merging uncertainty and representativeness, and propose an efficient alternating optimization method to solve it. With MCC, our method can eliminate the influence of outlier labels that are not discriminative to measure the uncertainty. To make further improvement on the ability of information measurement, we merge uncertainty and representativeness with the prediction labels of unknown data. It cannot only enhance the uncertainty but also improve the similarity measurement of multi-label data with labels information. Experiments on benchmark multi-label data sets have shown a superior performance than the state-of-the-art methods.

Antinuclear antibody (ANA) testing is a critical method for diagnosing autoimmune disorders such as Lupus, Sjögren's syndrome, and scleroderma. Despite its importance, manual ANA detection is slow, labor-intensive, and demands years of training. ANA detection is complicated by over 100 coexisting antibody types, resulting in vast fluorescent pattern combinations. Although machine learning and deep learning have enabled automation, ANA detection in real-world clinical settings presents unique challenges as it involves multi-instance, multi-label (MIML) learning. In this paper, a novel framework for ANA detection is proposed that handles the complexities of MIML tasks using unaltered microscope images without manual preprocessing. Inspired by human labeling logic, it identifies consistent ANA sub-regions and assigns aggregated labels accordingly. These steps are implemented using three task-specific components: an instance sampler, a probabilistic pseudo-label dispatcher, and self-paced weight learning rate coefficients. The instance sampler suppresses low-confidence instances by modeling pattern confidence, while the dispatcher adaptively assigns labels based on instance distinguishability. Self-paced learning adjusts training according to empirical label observations. Our framework overcomes limitations of traditional MIML methods and supports end-to-end optimization. Extensive experiments on one ANA dataset and three public medical MIML benchmarks demonstrate the superiority of our framework. On the ANA dataset, our model achieves up to +7.0% F1-Macro and +12.6% mAP gains over the best prior method, setting new state-of-the-art results. It also ranks top-2 across all key metrics on public datasets, reducing Hamming loss and one-error by up to 18.2% and 26.9%, respectively. The source code can be accessed at https://github.com/fletcherjiang/ANA-SelfPacedLearning.

For automatic object detection tasks, large amounts of training images are usually labeled to achieve more reliable training of the object classifiers; this is cost-expensive since it requires hiring professionals to label large-scale training images. When a large number of object classes come into view, the issue of obtaining a large enough amount of the labeled training images becomes more critical. There are three potential solutions to reduce the burden for image labeling: (1) allowing people to provide the object labels loosely at the image level rather than at the object level (e.g., loosely-tagged images without identifying the exact object locations in the images); (2) harnessing large-scale collaboratively-tagged images that are available on the Internet; and, (3) developing new machine learning algorithms that can directly leverage large-scale collaboratively- or loosely-tagged images for achieving more effective training of a large number of object classifiers. Based on these observations, a multi-task multi-label multiple instance learning (MTML-MIL) algorithm is developed in this paper by leveraging both interobject correlations and large-scale loosely-labeled images for object classifier training. By seamlessly integrating multi-task learning, multi-label learning, and multiple instance learning, our MTML-MIL algorithm can achieve more accurate training of a large number of inter-related object classifiers (where an object network is constructed for determining the inter-related learning tasks directly in the feature space rather than in the label space). Our experimental results have shown that our MTML-MIL algorithm can achieve higher detection accuracy rates for automatic object detection.

Tongue diagnosis characterization is a key research issue in the development of Traditional Chinese Medicine (TCM). Many kinds of information, such as tongue body color, coat color and coat thickness, can be reflected from a tongue image. That is, tongue images are multi-label data. However, traditional supervised learning is used to model single-label data. In this paper, multi-label learning is applied to the tongue image classification. Color features and texture features are extracted after separation of tongue coat and body, and multi-label learning algorithms are used for classification. Results showed LEAD (Multi-Label Learning by Exploiting Label Dependency), a multi-label learning algorithm demonstrating to exploit correlations among labels, is superior to the other multi-label algorithms. At last, the iteration algorithm is used to set an optimal threshold for each label to improve the results of LEAD. In this paper, we have provided an effective way for computer aided TCM diagnosis.