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High-throughput technologies and computational methods are transforming biology from a qualitative, descriptive discipline into a quantitative, multi-parameter field. The wealth of publically available “big data” has promoted a paradigm shift in medical research. With the increase of integrative efforts across disciplines, a higher emphasis has been put on using data to define and drive hypotheses. Through a synergistic coupling of molecular indexes from transcrip [Detail] ...
Recent advances in quantitative imaging and “omics” technology have generated a wealth of mineable biological “big data”. With the push towards a P4 “predictive, preventive, personalized, and participatory” approach to medicine, researchers began integrating complementary tools to further tune existing diagnostic and therapeutic models. The field of radiogenomics has long pioneered such multidisciplinary investigations in neuroscience and oncology, correlating genotypic and phenotypic signatures to study structural and functional changes in relation to altered molecular behavior. Given the innate dynamic nature of complex disorders and the role of environmental and epigenetic factors in pathogenesis, the transcriptome can further elucidate serial modifications undetected at the genome level. We therefore propose “radiotranscriptomics” as a new member of the P4 medicine initiative, combining transcriptome information, including gene expression and isoform variation, and quantitative image annotations.
We review our studies on how to identify the most appropriate models of diseases, and how to determine their parameters in a quantitative manner given a short time series of biomarkers, using intermittent androgen deprivation therapy of prostate cancer as an example. Recently, it has become possible to estimate the specific parameters of individual patients within a reasonable time by employing the information concerning other previous patients as a prior. We discuss the importance of using multiple mathematical methods simultaneously to achieve a solid diagnosis and prognosis in the future practice of personalized medicine.
Recent advances in next-generation sequencing technology allow high-throughput RNA sequencing (RNA-Seq) to be widely applied in transcriptomic studies. For model organisms with a reference genome, the first step in analysis of RNA-Seq data involves mapping of short-read sequences to the reference genome. Reference-guided transcriptome assembly is an optional step, which is recommended if the aim is to identify novel transcripts. Following read mapping, the primary interest of biologists in many RNA-Seq studies is the investigation of differential expression between experimental groups. In this review, we discuss recent developments in RNA-Seq data analysis applied to model organisms, including methods and algorithms for direct mapping, reference-guided transcriptome assembly and differential expression analysis, and provide insights for the future direction of RNA-Seq.
Owing to rapid advances in the next-generation sequencing technology, the cost of DNA sequencing has been reduced by over several orders of magnitude. However, genomic sequencing of individuals at the population scale is still restricted to a few model species due to the huge challenge of constructing libraries for thousands of samples. Meanwhile, pooled sequencing provides a cost-effective alternative to sequencing individuals separately, which could vastly reduce the time and cost for DNA library preparation. Technological improvements, together with the broad range of biological research questions that require large sample sizes, mean that pooled sequencing will continue to complement the sequencing of individual genomes and become increasingly important in the foreseeable future. However, simply mixing samples together for sequencing makes it impossible to identify reads that belongs to each sample. Barcoding technology could help to solve this problem, nonetheless, currently, barcoding every sample is costly especially for large-scale samples. An alternative to barcoding is combinatorial pooled sequencing which employs pooling pattern rather than short DNA barcodes to encode each sample. In combinatorial pooled sequencing, samples are mixed into few pools according to a carefully designed pooling strategy which allows the sequencing data to be decoded to identify the reads that belongs to the sample that are unique or rare in the population. In this review, we mainly survey the experiment design and decoding procedure for the combinatorial pooled sequencing applied in rare variant and rare haplotype carriers screening, complex genome assembling and single individual haplotyping.
MicroRNA (miRNA) plays key roles in post-transcriptional regulations. Recently, a competing endogenous RNA (ceRNA) hypothesis has been proposed that miRNA targets could communicate and regulate each other through titrating shared miRNAs, which provides a new layer of gene regulation. Though a number of ceRNAs playing biological functions have been identified, the ceRNA hypothesis remains controversial. Recent experimental and theoretical studies argued that the modulation of a single RNA species could hardly change the expression level of competing miRNA targets through ceRNA effect under normal physiological conditions. Here, we reviewed a common framework to model miRNA regulations, and summarized the current theoretical and experimental studies for quantitative understanding ceRNA effect. By revisiting a coarse-grained ceRNA model, we proposed that network topology could significantly influence the competing effect and ceRNA regulation at protein level could be much stronger than that at RNA level. We also provided a conditional independent binding equation to describe miRNA relative repression on different target, which could be applied to quantify siRNA off-target effect.
One goal of precise oncology is to re-classify cancer based on molecular features rather than its tissue origin. Integrative clustering of large-scale multi-omics data is an important way for molecule-based cancer classification. The data heterogeneity and the complexity of inter-omics variations are two major challenges for the integrative clustering analysis. According to the different strategies to deal with these difficulties, we summarized the clustering methods as three major categories: direct integrative clustering, clustering of clusters and regulatory integrative clustering. A few practical considerations on data pre-processing, post-clustering analysis and pathway-based analysis are also discussed.
