April 2016

Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self tolerance and inflammatory responses. Recent studies have revealed a discrete mode of T cell receptor (TCR) signalling that regulates TReg cell differentiation, maintenance and function and that affects gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of TReg cells in the context of their function in health and disease...

No abstract text is available yet for this article.

Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of individual genes.

High-throughput bioinformatic analyses increasingly rely on pipeline frameworks to process sequence and metadata. Modern implementations of these frameworks differ on three key dimensions: using an implicit or explicit syntax, using a configuration, convention or class-based design paradigm and offering a command line or workbench interface. Here I survey and compare the design philosophies of several current pipeline frameworks. I provide practical recommendations based on analysis requirements and the user base...

T cells have a pivotal protective role in defense against infection and cancer but also are instrumental in the development of many autoimmune diseases. The regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation, and manipulating metabolic pathways in these cells can alter their function and longevity. While the importance of T cell metabolic remodeling in different physiological settings is not fully understood, there is a growing realization that inappropriate metabolic remodeling underlies many aberrant immune responses and that manipulating cellular metabolism can beneficially enhance or temper immunity...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Precision medicine initiatives come amid the rapid growth in quantity and variety of biomedical data, which exceeds the capacity of matrix-oriented data representations and many current analysis algorithms. Tensor factorizations extend the matrix view to multiple modalities and support dimensionality reduction methods that identify latent groups of data for meaningful summarization of both features and instances. In this opinion article, we analyze the modest literature on applying tensor factorization to various biomedical fields including genotyping and phenotyping...

There is a clear demand for hands-on bioinformatics training. The development of bioinformatics workshop content is both time-consuming and expensive. Therefore, enabling trainers to develop bioinformatics workshops in a way that facilitates reuse is becoming increasingly important. The most widespread practice for sharing workshop content is through making PDF, PowerPoint and Word documents available online. While this effort is to be commended, such content is usually not so easy to reuse or repurpose and does not capture all the information required for a third party to rerun a workshop...

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis can detect protein/DNA-binding and histone-modification sites across an entire genome. Recent advances in sequencing technologies and analyses enable us to compare hundreds of samples simultaneously; such large-scale analysis has potential to reveal the high-dimensional interrelationship level for regulatory elements and annotate novel functional genomic regions de novo. Because many experimental considerations are relevant to the choice of a method in a ChIP-seq analysis, the overall design and quality management of the experiment are of critical importance...

Journal-based science communication is not accessible or comprehensible to a general public curious about science and eager for the next wave of scientific innovation. We propose an alternative medium for scientists to communicate their work to the general public in an engaging and digestible way through the use of whiteboard videos. We describe the process of producing science whiteboard videos and the benefits and challenges therein.

Communicating science and being an advocate for public support of research are critical roles for scientists. However, despite having the most relevant expertise, many of us do not get involved in matters bridging science and policy. Here I discuss the importance of science advocacy by researchers, and present strategies for communicating the relevance of your work to the public and elected officials, including the crafting of a two-minute pitch - a valuable skill for all scientists.

Proficiency in art and illustration was once considered an essential skill for biologists, because text alone often could not suffice to describe observations of biological systems. With modern imaging technology, it is no longer necessary to illustrate what we can see by eye. However, in molecular and cellular biology, our understanding of biological processes is dependent on our ability to synthesize diverse data to generate a hypothesis. Creating visual models of these hypotheses is important for generating new ideas and for communicating to our peers and to the public...

No abstract text is available yet for this article.

Cancer heterogeneity, a hallmark enabling clonal survival and therapy resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T-cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that, if better harnessed, could significantly enhance the efficacy of cytotoxic therapy and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled...

Although they are classically viewed as continuously recirculating through the lymphoid organs and blood, lymphocytes also establish residency in non-lymphoid tissues, most prominently at barrier sites, including the mucosal surfaces and skin. These specialized tissue-resident lymphocyte subsets span the innate-adaptive continuum and include innate lymphoid cells (ILCs), unconventional T cells (e.g., NKT, MAIT, γδ T cells, and CD8αα(+) IELs), and tissue-resident memory T (T(RM)) cells. Although these diverse cell types differ in the particulars of their biology, they nonetheless exhibit important shared features, including a role in the preservation of tissue integrity and function during homeostasis, infection, and non-infectious perturbations...

Transcriptional regulatory networks (TRNs) encode instructions for animal development and physiological responses. Recent advances in genomic technologies and computational modeling have revolutionized our ability to construct models of TRNs. Here, we survey current computational methods for inferring TRN models using genome-scale data. We discuss their advantages and limitations. We summarize representative TRNs constructed using genome-scale data in both normal and disease development. We discuss lessons learned about the structure/function relationship of TRNs, based on examining various large-scale TRN models...

T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet...

Long noncoding RNAs (lncRNAs) are emerging as a class of important regulators participating in various biological functions and disease processes. With the widespread application of next-generation sequencing technologies, large numbers of lncRNAs have been identified, producing plenty of lncRNA annotation resources in different contexts. However, at present, we lack a comprehensive overview of these lncRNA annotation resources. In this study, we reviewed 24 currently available lncRNA annotation resources referring to > 205 000 lncRNAs in over 50 tissues and cell lines...

Given that the majority of multi-exon genes generate diverse functional products, it is important to evaluate expression at the isoform level. Previous studies have demonstrated strong gene-level correlations between RNA sequencing (RNA-seq) and microarray platforms, but have not studied their concordance at the isoform level. We performed transcript abundance estimation on raw RNA-seq and exon-array expression profiles available for common glioblastoma multiforme samples from The Cancer Genome Atlas using different analysis pipelines, and compared both the isoform- and gene-level expression estimates between programs and platforms...