Next-Generation Pathology
The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient’s tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanis...
Source: Springer protocols feed by Bioinformatics - December 21, 2015 Category: Bioinformatics Source Type: news

Systems Medicine: The Future of Medical Genomics, Healthcare, and Wellness
Recent advances in genomics have led to the rapid and relatively inexpensive collection of patient molecular data including multiple types of omics data. The integration of these data with clinical measurements has the potential to impact on our understanding of the molecular basis of disease and on disease management. Systems medicine is an approach to understanding disease through an integration of large patient datasets. It offers the possibility for personalized strategies for healthcare through the development of a new taxonomy of disease. Advanced computing will be an important component in effectively implementing s...
Source: Springer protocols feed by Bioinformatics - December 21, 2015 Category: Bioinformatics Source Type: news

Taking Bioinformatics to Systems Medicine
Systems medicine promotes a range of approaches and strategies to study human health and disease at a systems level with the aim of improving the overall well-being of (healthy) individuals, and preventing, diagnosing, or curing disease. In this chapter we discuss how bioinformatics critically contributes to systems medicine. First, we explain the role of bioinformatics in the management and analysis of data. In particular we show the importance of publicly available biological and clinical repositories to support systems medicine studies. Second, we discuss how the integration and analysis of multiple types of omics data ...
Source: Springer protocols feed by Bioinformatics - December 21, 2015 Category: Bioinformatics Source Type: news

Systems Medicine: Sketching the Landscape
To understand the meaning of the term Systems Medicine and to distinguish it from seemingly related other expressions currently in use, such as precision, personalized, -omics, or big data medicine, its underlying history and development into present time needs to be highlighted. Having this development in mind, it becomes evident that Systems Medicine is a genuine concept as well as a novel way of tackling the manifold complexity that occurs in nowadays clinical medicine—and not just a rebranding of what has previously been done in the past. So looking back it seems clear to many in the field that Systems Medicine h...
Source: Springer protocols feed by Bioinformatics - December 21, 2015 Category: Bioinformatics Source Type: news

Computational Design of Artificial RNA Molecules for Gene Regulation
RNA interference (RNAi) is a powerful tool for the regulation of gene expression. Small exogenous noncoding RNAs (ncRNAs) such as siRNA and shRNA are the active silencing agents, intended to target and cleave complementary mRNAs in a specific way. They are widely and successfully employed in functional studies, and several ongoing and already completed siRNA-based clinical trials suggest encouraging results in the regulation of overexpressed genes in disease. (Source: Springer protocols feed by Bioinformatics)
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Analysis of Alternative Splicing Events in Custom Gene Datasets by AStalavista
Alternative splicing (AS) is a eukaryotic principle to derive more than one RNA product from transcribed genes by removing distinct subsets of introns from a premature polymer. We know today that this process is highly regulated and makes up a large part of the differences between species, cell types, and states. The key to compare AS across different genes or organisms is to tokenize the AS phenomenon into atomary units, so-called AS events. These events then usually are grouped by common patterns to investigate the underlying molecular mechanisms that drive their regulation. However, attempts to decompose loci with AS ob...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

ASPicDB: A Database Web Tool for Alternative Splicing Analysis
Alternative splicing (AS) is a basic molecular phenomenon that increases the functional complexity of higher eukaryotic transcriptomes. Indeed, through AS individual gene loci can generate multiple RNAs from the same pre-mRNA. AS has been investigated in a variety of clinical and pathological studies, such as the transcriptome regulation in cancer. In human, recent works based on massive RNA sequencing indicate that >95 % of pre-mRNAs are processed to yield multiple transcripts. Given the biological relevance of AS, several computational efforts have been done leading to the implementation of novel algorithms and specif...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Rfam: Annotating Families of Non-Coding RNA Sequences
The primary task of the Rfam database is to collate experimentally validated noncoding RNA (ncRNA) sequences from the published literature and facilitate the prediction and annotation of new homologues in novel nucleotide sequences. We group homologous ncRNA sequences into “families” and related families are further grouped into “clans.” We collate and manually curate data cross-references for these families from other databases and external resources. Our Web site offers researchers a simple interface to Rfam and provides tools with which to annotate their own sequences using our covariance models ...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

A Guideline for the Annotation of UTR Regulatory Elements in the UTRsite Collection
Gene expression regulatory elements are scattered in gene promoters and pre-mRNAs. In particular, RNA elements lying in untranslated regions (5′ and 3′UTRs) are poorly studied because of their peculiar features (i.e., a combination of primary and secondary structure elements) which also pose remarkable computational challenges. Several years ago, we began collecting experimentally characterized UTR regulatory elements, developing the specialized database UTRsite. This paper describes the detailed guidelines to annotate cis-regulatory elements in 5′ and 3′ UnTranslated Regions (UTRs) by computational...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Exploring the RNA Editing Potential of RNA-Seq Data by ExpEdit
Revealing the impact of A-to-I RNA editing in RNA-Seq experiments is relevant in humans because RNA editing can influence gene expression. In addition, its deregulation has been linked to a variety of human diseases. Exploiting the RNA editing potential in complete RNA-Seq datasets, however, is a challenging task. Indeed, no dedicated software is available, and sometimes deep computational skills and appropriate hardware resources are required. To explore the impact of known RNA editing events in massive transcriptome sequencing experiments, we developed the ExpEdit web service application. In the present work, we provide ...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

The ViennaRNA Web Services
The ViennaRNA package is a widely used collection of programs for thermodynamic RNA secondary structure prediction. Over the years, many additional tools have been developed building on the core programs of the package to also address issues related to noncoding RNA detection, RNA folding kinetics, or efficient sequence design considering RNA-RNA hybridizations. The ViennaRNA web services provide easy and user-friendly web access to these tools. This chapter describes how to use this online platform to perform tasks such as prediction of minimum free energy structures, prediction of RNA-RNA hybrids, or noncoding RNA detect...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Accurate Mapping of RNA-Seq Data
The mapping of RNA-Seq data on genome is not the same as DNA-Seq data, because the junction reads span two exons and have no identical matches at reference genome. In this chapter, we describe a junction read aligner SpliceMap that is based on an algorithm of “half-read seeding” and “seeding extension.” Four analysis steps are integrated in SpliceMap (half-read mapping, seeding selection, seeding extension and junction search, and paired-end filtering), and all toning parameters of these steps can be editable in a single configuration file. Thus, SpliceMap can be executed by a single command. While ...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Quality Control of RNA-Seq Experiments
Direct sequencing of the complementary DNA (cDNA) using high-throughput sequencing technologies (RNA-seq) is widely used and allows for more comprehensive understanding of the transcriptome than microarray. In theory, RNA-seq should be able to precisely identify and quantify all RNA species, small or large, at low or high abundance. However, RNA-seq is a complicated, multistep process involving reverse transcription, amplification, fragmentation, purification, adaptor ligation, and sequencing. Improper operations at any of these steps could make biased or even unusable data. Additionally, RNA-seq intrinsic biases (such as ...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

RIP-Seq Data Analysis to Determine RNA–Protein Associations
Next-generation sequencing (NGS) technologies have opened new avenues of unprecedented power for research in molecular biology and genetics. In particular, their application to the study of RNA-binding proteins (RBPs), extracted through immunoprecipitation (RIP), permits to sequence and characterize all RNAs that were found to be bound in vivo by a given RBP (RIP-Seq). On the other hand, NGS-based experiments, including RIP-Seq, produce millions of short sequence fragments that have to be processed with suitable bioinformatic tools and methods to recover and/or quantify the original sequence sample. In this chapter we prov...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news

Deciphering Metatranscriptomic Data
Metatranscriptomic data contributes another piece of the puzzle to understanding the phylogenetic structure and function of a community of organisms. High-quality total RNA is a bountiful mixture of ribosomal, transfer, messenger and other noncoding RNAs, where each family of RNA is vital to answering questions concerning the hidden microbial world. Software tools designed for deciphering metatranscriptomic data fall under two main categories: the first is to reassemble millions of short nucleotide fragments produced by high-throughput sequencing technologies into the original full-length transcriptomes for all organisms w...
Source: Springer protocols feed by Bioinformatics - January 1, 2015 Category: Bioinformatics Source Type: news