Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Pattern Recognition and Machine Learning

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

PL02-05 

All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Patterns of Somatic Mutation in Human Cancer Genomes

Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated.

Physiological and pathological roles for microRNAs in the immune system

https://iridia.ulb.ac.be/IridiaTrSeries/link/IridiaTr2011-004.pdf

The irace package: Iterated racing for automatic algorithm configuration

In the era of big data, transformation of biomedical big data into valuable knowledge has been one of the most important challenges in bioinformatics. Deep learning has advanced rapidly since the early 2000s and now demonstrates state-of-the-art performance in various fields. Accordingly, application of deep learning in bioinformatics to gain insight from data has been emphasized in both academia and industry. Here, we review deep learning in bioinformatics, presenting examples of current research. To provide a useful and comprehensive perspective, we categorize research both by the bioinformatics domain (i.e. omics, biomedical imaging, biomedical signal processing) and deep learning architecture (i.e. deep neural networks, convolutional neural networks, recurrent neural networks, emergent architectures) and present brief descriptions of each study. Additionally, we discuss theoretical and practical issues of deep learning in bioinformatics and suggest future research directions. We believe that this review will provide valuable insights and serve as a starting point for researchers to apply deep learning approaches in their bioinformatics studies.

Deep learning in bioinformatics

This article reviews machine learning methods for bioinformatics. It presents modelling methods, such as supervised classification, clustering and probabilistic graphical models for knowledge discovery, as well as deterministic and stochastic heuristics for optimization. Applications in genomics, proteomics, systems biology, evolution and text mining are also shown.

/pdf/machine-learning-in-bioinformatics-5gfm1x1ssk.pdf

Machine learning in bioinformatics

Differences in gene expression patterns have been documented not only in Multiple Sclerosis patients versus healthy controls but also in the relapse of the disease. Recently a new gene expression modulator has been identified: the microRNA or miRNA. The aim of this work is to analyze the possible role of miRNAs in multiple sclerosis, focusing on the relapse stage. We have analyzed the expression patterns of 364 miRNAs in PBMC obtained from multiple sclerosis patients in relapse status, in remission status and healthy controls. The expression patterns of the miRNAs with significantly different expression were validated in an independent set of samples. In order to determine the effect of the miRNAs, the expression of some predicted target genes of these were studied by qPCR. Gene interaction networks were constructed in order to obtain a co-expression and multivariate view of the experimental data. The data analysis and later validation reveal that two miRNAs (hsa-miR-18b and hsa-miR-599) may be relevant at the time of relapse and that another miRNA (hsa-miR-96) may be involved in remission. The genes targeted by hsa-miR-96 are involved in immunological pathways as Interleukin signaling and in other pathways as wnt signaling. This work highlights the importance of miRNA expression in the molecular mechanisms implicated in the disease. Moreover, the proposed involvement of these small molecules in multiple sclerosis opens up a new therapeutic approach to explore and highlight some candidate biomarker targets in MS.

/pdf/differential-micro-rna-expression-in-pbmc-from-multiple-1ajh1l7vlq.pdf

Differential micro RNA expression in PBMC from multiple sclerosis patients.

Comparing the results obtained by two or more algorithms in a set of problems is a central task in areas such as machine learning or optimization. Drawing conclusions from these comparisons may require the use of statistical tools such as hypothesis testing. There are some interesting papers that cover this topic. In this manuscript we present scmamp, an R package aimed at being a tool that simplifies the whole process of analyzing the results obtained when comparing algorithms, from loading the data to the production of plots and tables. Comparing the performance of different algorithms is an essential step in many research and practical computational works. When new algorithms are proposed, they have to be compared with the state of the art. Similarly, when an algorithm is used for a particular problem, its performance with different sets of parameters has to be compared, in order to tune them for the best results. When the differences are very clear (e.g., when an algorithm is the best in all the problems used in the comparison), the direct comparison of the results may be enough. However, this is an unusual situation and, thus, in most situations a direct comparison may be misleading and not enough to draw sound conclusions; in those cases, the statistical assessment of the results is advisable. The statistical comparison of algorithms in the context of machine learning has been covered in several papers. In particular, the tools implemented in this package are those presented in Demšar (2006); García and Herrera (2008); García et al. (2010). Another good review that covers, among other aspects, the statistical assessment of the results in the context of supervised classification can be found in Santafé et al. (2015).

/pdf/scmamp-statistical-comparison-of-multiple-algorithms-in-d5te89rd9g.pdf

scmamp: statistical comparison of multiple algorithms in multiple problems

The increase in the number and complexity of biological databases has raised the need for modern and powerful data analysis tools and techniques. In order to fulfill these requirements, the machine learning discipline has become an everyday tool in bio-laboratories. The use of machine learning techniques has been extended to a wide spectrum of bioinformatics applications. It is broadly used to investigate the underlying mechanisms and interactions between biological molecules in many diseases, and it is an essential tool in any biomarker discovery process. In this chapter, we provide a basic taxonomy of machine learning algorithms, and the characteristics of main data preprocessing, supervised classification, and clustering techniques are shown. Feature selection, classifier evaluation, and two supervised classification topics that have a deep impact on current bioinformatics are presented. We make the interested reader aware of a set of popular web resources, open source software tools, and benchmarking data repositories that are frequently used by the machine learning community.

https://www.springer.com/cda/content/document/cda_downloaddocument/9781603271936-c1.pdf?SGWID=0-0-45-835310-p173739853

Borja Calvo

Papers

Machine learning in bioinformatics

Differential micro RNA expression in PBMC from multiple sclerosis patients.

scmamp: statistical comparison of multiple algorithms in multiple problems

Machine learning: an indispensable tool in bioinformatics.

Learning Bayesian classifiers from positive and unlabeled examples