1,678 research outputs found
Combining learning and constraints for genome-wide protein annotation
BackgroundThe advent of high-throughput experimental techniques paved the way to genome-wide computational analysis and predictive annotation studies. When considering the joint annotation of a large set of related entities, like all proteins of a certain genome, many candidate annotations could be inconsistent, or very unlikely, given the existing knowledge. A sound predictive framework capable of accounting for this type of constraints in making predictions could substantially contribute to the quality of machine-generated annotations at a genomic scale.ResultsWe present Ocelot, a predictive pipeline which simultaneously addresses functional and interaction annotation of all proteins of a given genome. The system combines sequence-based predictors for functional and protein-protein interaction (PPI) prediction with a consistency layer enforcing (soft) constraints as fuzzy logic rules. The enforced rules represent the available prior knowledge about the classification task, including taxonomic constraints over each GO hierarchy (e.g. a protein labeled with a GO term should also be labeled with all ancestor terms) as well as rules combining interaction and function prediction. An extensive experimental evaluation on the Yeast genome shows that the integration of prior knowledge via rules substantially improves the quality of the predictions. The system largely outperforms GoFDR, the only high-ranking system at the last CAFA challenge with a readily available implementation, when GoFDR is given access to intra-genome information only (as Ocelot), and has comparable or better results (depending on the hierarchy and performance measure) when GoFDR is allowed to use information from other genomes. Our system also compares favorably to recent methods based on deep learning
Multi-Target Prediction: A Unifying View on Problems and Methods
Multi-target prediction (MTP) is concerned with the simultaneous prediction
of multiple target variables of diverse type. Due to its enormous application
potential, it has developed into an active and rapidly expanding research field
that combines several subfields of machine learning, including multivariate
regression, multi-label classification, multi-task learning, dyadic prediction,
zero-shot learning, network inference, and matrix completion. In this paper, we
present a unifying view on MTP problems and methods. First, we formally discuss
commonalities and differences between existing MTP problems. To this end, we
introduce a general framework that covers the above subfields as special cases.
As a second contribution, we provide a structured overview of MTP methods. This
is accomplished by identifying a number of key properties, which distinguish
such methods and determine their suitability for different types of problems.
Finally, we also discuss a few challenges for future research
A Comparative Study of Pairwise Learning Methods based on Kernel Ridge Regression
Many machine learning problems can be formulated as predicting labels for a
pair of objects. Problems of that kind are often referred to as pairwise
learning, dyadic prediction or network inference problems. During the last
decade kernel methods have played a dominant role in pairwise learning. They
still obtain a state-of-the-art predictive performance, but a theoretical
analysis of their behavior has been underexplored in the machine learning
literature.
In this work we review and unify existing kernel-based algorithms that are
commonly used in different pairwise learning settings, ranging from matrix
filtering to zero-shot learning. To this end, we focus on closed-form efficient
instantiations of Kronecker kernel ridge regression. We show that independent
task kernel ridge regression, two-step kernel ridge regression and a linear
matrix filter arise naturally as a special case of Kronecker kernel ridge
regression, implying that all these methods implicitly minimize a squared loss.
In addition, we analyze universality, consistency and spectral filtering
properties. Our theoretical results provide valuable insights in assessing the
advantages and limitations of existing pairwise learning methods.Comment: arXiv admin note: text overlap with arXiv:1606.0427
An Attention-based Collaboration Framework for Multi-View Network Representation Learning
Learning distributed node representations in networks has been attracting
increasing attention recently due to its effectiveness in a variety of
applications. Existing approaches usually study networks with a single type of
proximity between nodes, which defines a single view of a network. However, in
reality there usually exists multiple types of proximities between nodes,
yielding networks with multiple views. This paper studies learning node
representations for networks with multiple views, which aims to infer robust
node representations across different views. We propose a multi-view
representation learning approach, which promotes the collaboration of different
views and lets them vote for the robust representations. During the voting
process, an attention mechanism is introduced, which enables each node to focus
on the most informative views. Experimental results on real-world networks show
that the proposed approach outperforms existing state-of-the-art approaches for
network representation learning with a single view and other competitive
approaches with multiple views.Comment: CIKM 201
Bio-JOIE: Joint Representation Learning of Biological Knowledge Bases
The widespread of Coronavirus has led to a worldwide pandemic with a high
mortality rate. Currently, the knowledge accumulated from different studies
about this virus is very limited. Leveraging a wide-range of biological
knowledge, such as gene ontology and protein-protein interaction (PPI) networks
from other closely related species presents a vital approach to infer the
molecular impact of a new species. In this paper, we propose the transferred
multi-relational embedding model Bio-JOIE to capture the knowledge of gene
ontology and PPI networks, which demonstrates superb capability in modeling the
SARS-CoV-2-human protein interactions. Bio-JOIE jointly trains two model
components. The knowledge model encodes the relational facts from the protein
and GO domains into separated embedding spaces, using a hierarchy-aware
encoding technique employed for the GO terms. On top of that, the transfer
model learns a non-linear transformation to transfer the knowledge of PPIs and
gene ontology annotations across their embedding spaces. By leveraging only
structured knowledge, Bio-JOIE significantly outperforms existing
state-of-the-art methods in PPI type prediction on multiple species.
Furthermore, we also demonstrate the potential of leveraging the learned
representations on clustering proteins with enzymatic function into enzyme
commission families. Finally, we show that Bio-JOIE can accurately identify
PPIs between the SARS-CoV-2 proteins and human proteins, providing valuable
insights for advancing research on this new disease.Comment: ACM BCB 2020, Best Student Pape
VB-MK-LMF: Fusion of drugs, targets and interactions using Variational Bayesian Multiple Kernel Logistic Matrix Factorization
Background
Computational fusion approaches to drug-target interaction (DTI) prediction, capable of utilizing multiple sources of background knowledge, were reported to achieve superior predictive performance in multiple studies. Other studies showed that specificities of the DTI task, such as weighting the observations and focusing the side information are also vital for reaching top performance.
Method
We present Variational Bayesian Multiple Kernel Logistic Matrix Factorization (VB-MK-LMF), which unifies the advantages of (1) multiple kernel learning, (2) weighted observations, (3) graph Laplacian regularization, and (4) explicit modeling of probabilities of binary drug-target interactions.
Results
VB-MK-LMF achieves significantly better predictive performance in standard benchmarks compared to state-of-the-art methods, which can be traced back to multiple factors. The systematic evaluation of the effect of multiple kernels confirm their benefits, but also highlights the limitations of linear kernel combinations, already recognized in other fields. The analysis of the effect of prior kernels using varying sample sizes sheds light on the balance of data and knowledge in DTI tasks and on the rate at which the effect of priors vanishes. This also shows the existence of ``small sample size'' regions where using side information offers significant gains. Alongside favorable predictive performance, a notable property of MF methods is that they provide a unified space for drugs and targets using latent representations. Compared to earlier studies, the dimensionality of this space proved to be surprisingly low, which makes the latent representations constructed by VB-ML-LMF especially well-suited for visual analytics. The probabilistic nature of the predictions allows the calculation of the expected values of hits in functionally relevant sets, which we demonstrate by predicting drug promiscuity. The variational Bayesian approximation is also implemented for general purpose graphics processing units yielding significantly improved computational time.
Conclusion
In standard benchmarks, VB-MK-LMF shows significantly improved predictive performance in a wide range of settings. Beyond these benchmarks, another contribution of our work is highlighting and providing estimates for further pharmaceutically relevant quantities, such as promiscuity, druggability and total number of interactions.
Availability
Data and code are available at http://bioinformatics.mit.bme.hu
Prediction of lncRNA-Disease Associations Based on Inductive Matrix Completion
Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNAâdisease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNAâdisease associations, especially for novel lncRNAs, remains challenging.
Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNAâ disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNAâdisease interactions and functional similarity of diseases based on diseaseâgene and geneâgene onotology associations. Then, we extract primary feature vectors from Gaussian interaction profile kernel of lncRNAs and functional similarity of diseases by principal component analysis, respectively. For a new lncRNA, we calculate the interaction profile according to the interaction profiles of its neighbors. At last, we complete the association matrix based on the inductive matrix completion framework using the primary feature vectors from the constructed feature matrices. Computational results show that SIMCLDA can effectively predict lncRNAâdisease associations with higher accuracy compared with previous methods. Furthermore, case studies show that SIMCLDA can effectively predict candidate lncRNAs for renal cancer, gastric cancer and prostate cancer
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