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Genome Biology

Miri Danan-Gotthold, Clotilde Guyon, Matthieu Giraud, Erez Y Levanon, Jakub Abramson
BACKGROUND: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells that have a unique capacity to express, and subsequently present, a large fraction of body antigens. While the scope of promiscuously expressed genes by medullary thymic epithelial cells is well-established, relatively little is known about the expression of variants that are generated by co-transcriptional and post-transcriptional processes...
October 24, 2016: Genome Biology
Etienne Becht, Nicolas A Giraldo, Laetitia Lacroix, Bénédicte Buttard, Nabila Elarouci, Florent Petitprez, Janick Selves, Pierre Laurent-Puig, Catherine Sautès-Fridman, Wolf H Fridman, Aurélien de Reyniès
We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two stromal cell populations in heterogeneous tissues from transcriptomic data. We present in vitro mRNA mixture and ex vivo immunohistochemical data that quantitatively support the validity of our method's estimates. Additionally, we demonstrate that MCP-counter overcomes several limitations or weaknesses of previously proposed computational approaches...
October 20, 2016: Genome Biology
Juntao Liu, Ting Yu, Tao Jiang, Guojun Li
Transcriptome assemblers aim to reconstruct full-length transcripts from RNA-seq data. We present TransComb, a genome-guided assembler developed based on a junction graph, weighted by a bin-packing strategy and paired-end information. A newly designed extension method based on weighted junction graphs can accurately extract paths representing expressed transcripts, whether they have low or high expression levels. Tested on both simulated and real datasets, TransComb demonstrates significant improvements in both recall and precision over leading assemblers, including StringTie, Cufflinks, Bayesembler, and Traph...
October 19, 2016: Genome Biology
Justine Debelius, Se Jin Song, Yoshiki Vazquez-Baeza, Zhenjiang Zech Xu, Antonio Gonzalez, Rob Knight
Many factors affect the microbiomes of humans, mice, and other mammals, but substantial challenges remain in determining which of these factors are of practical importance. Considering the relative effect sizes of both biological and technical covariates can help improve study design and the quality of biological conclusions. Care must be taken to avoid technical bias that can lead to incorrect biological conclusions. The presentation of quantitative effect sizes in addition to P values will improve our ability to perform meta-analysis and to evaluate potentially relevant biological effects...
October 19, 2016: Genome Biology
Kevin A McGoff, Xin Guo, Anastasia Deckard, Christina M Kelliher, Adam R Leman, Lauren J Francey, John B Hogenesch, Steven B Haase, John L Harer
We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, sizes, and degrees of complexity. Moreover, we demonstrate its ability to incorporate biological prior information and make informative predictions on a well-characterized in vivo system using data from budding yeast that have been synchronized in the cell cycle...
October 19, 2016: Genome Biology
Luca Giorgetti, Edith Heard
Chromosome conformation capture (3C)-based techniques have revolutionized the field of nuclear organization, partly replacing DNA FISH as the method of choice for studying three-dimensional chromosome architecture. Although DNA FISH is commonly used for confirming 3C-based findings, the two techniques are conceptually and technically different and comparing their results is not trivial. Here, we discuss both 3C-based techniques and DNA FISH approaches to highlight their similarities and differences. We then describe the technical biases that affect each approach, and review the available reports that address their compatibility...
October 19, 2016: Genome Biology
Brock C Christensen, Karl T Kelsey
A new mitotic clock and mathematical approach that incorporates DNA methylation biology common among human cell types provides a new tool for cancer epigenetics research.
October 19, 2016: Genome Biology
Ling-Ling Chen, Katrina G Claw, Sohini Ramachandran
What can be done to encourage and support women of color in STEM fields? Genome Biology spoke with three women of color who have had success in the area of genomics research.
October 11, 2016: Genome Biology
Björn Pietzenuk, Catarine Markus, Hervé Gaubert, Navratan Bagwan, Aldo Merotto, Etienne Bucher, Ales Pecinka
BACKGROUND: The mobilization of transposable elements (TEs) is suppressed by host genome defense mechanisms. Recent studies showed that the cis-regulatory region of Arabidopsis thaliana COPIA78/ONSEN retrotransposons contains heat-responsive elements (HREs), which cause their activation during heat stress. However, it remains unknown whether this is a common and potentially conserved trait and how it has evolved. RESULTS: We show that ONSEN, COPIA37, TERESTRA, and ROMANIAT5 are the major families of heat-responsive TEs in A...
October 11, 2016: Genome Biology
Anna K Knight, Jeffrey M Craig, Christiane Theda, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S Hansen, Mads V Hollegaard, David M Hougaard, Preben B Mortensen, Shantel M Weinsheimer, Thomas M Werge, Patricia A Brennan, Joseph F Cubells, D Jeffrey Newport, Zachary N Stowe, Jeanie L Y Cheong, Philippa Dalach, Lex W Doyle, Yuk J Loke, Andrea A Baccarelli, Allan C Just, Robert O Wright, Mara M Téllez-Rojo, Katherine Svensson, Letizia Trevisi, Elizabeth M Kennedy, Elisabeth B Binder, Stella Iurato, Darina Czamara, Katri Räikkönen, Jari M T Lahti, Anu-Katriina Pesonen, Eero Kajantie, Pia M Villa, Hannele Laivuori, Esa Hämäläinen, Hea Jin Park, Lynn B Bailey, Sasha E Parets, Varun Kilaru, Ramkumar Menon, Steve Horvath, Nicole R Bush, Kaja Z LeWinn, Frances A Tylavsky, Karen N Conneely, Alicia K Smith
BACKGROUND: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. RESULTS: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples...
October 7, 2016: Genome Biology
J Bohlin, S E Håberg, P Magnus, S E Reese, H K Gjessing, M C Magnus, C L Parr, C M Page, S J London, W Nystad
BACKGROUND: We explored the association between gestational age and cord blood DNA methylation at birth and whether DNA methylation could be effective in predicting gestational age due to limitations with the presently used methods. We used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa 1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both ultrasound and the last menstrual period...
October 7, 2016: Genome Biology
Ruth Pidsley, Elena Zotenko, Timothy J Peters, Mitchell G Lawrence, Gail P Risbridger, Peter Molloy, Susan Van Djik, Beverly Muhlhausler, Clare Stirzaker, Susan J Clark
BACKGROUND: In recent years the Illumina HumanMethylation450 (HM450) BeadChip has provided a user-friendly platform to profile DNA methylation in human samples. However, HM450 lacked coverage of distal regulatory elements. Illumina have now released the MethylationEPIC (EPIC) BeadChip, with new content specifically designed to target these regions. We have used HM450 and whole-genome bisulphite sequencing (WGBS) to perform a critical evaluation of the new EPIC array platform. RESULTS: EPIC covers over 850,000 CpG sites, including >90 % of the CpGs from the HM450 and an additional 413,743 CpGs...
October 7, 2016: Genome Biology
Michael Seifert, Betty Friedrich, Andreas Beyer
It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis...
October 3, 2016: Genome Biology
Zhen Yang, Andrew Wong, Diana Kuh, Dirk S Paul, Vardhman K Rakyan, R David Leslie, Shijie C Zheng, Martin Widschwendter, Stephan Beck, Andrew E Teschendorff
BACKGROUND: Variation in cancer risk among somatic tissues has been attributed to variations in the underlying rate of stem cell division. For a given tissue type, variable cancer risk between individuals is thought to be influenced by extrinsic factors which modulate this rate of stem cell division. To date, no molecular mitotic clock has been developed to approximate the number of stem cell divisions in a tissue of an individual and which is correlated with cancer risk. RESULTS: Here, we integrate mathematical modeling with prior biological knowledge to construct a DNA methylation-based age-correlative model which approximates a mitotic clock in both normal and cancer tissue...
October 3, 2016: Genome Biology
Mingxiang Teng, Michael I Love, Carrie A Davis, Sarah Djebali, Alexander Dobin, Brenton R Graveley, Sheng Li, Christopher E Mason, Sara Olson, Dmitri Pervouchine, Cricket A Sloan, Xintao Wei, Lijun Zhan, Rafael A Irizarry
No abstract text is available yet for this article.
September 30, 2016: Genome Biology
David W Cescon, Benjamin Haibe-Kains
APOBEC cytidine deaminases have been implicated as major contributors to the mutation burden in many cancers on the basis of their mutational signature. A new experimental study sheds light on the inciting factors, linking APOBEC3B expression to oncogene- and drug-induced replication stress.
September 30, 2016: Genome Biology
Hyongbum Kim
Peer reviewers are the unsung heroes of science. We celebrate reviewers through a series of interviews with people who have made particularly strong recent contributions to Genome Biology as reviewers. The first interview is with Hyongbum (Henry) Kim, an Associate Professor at Yonsei University College of Medicine in South Korea.
September 29, 2016: Genome Biology
Bradlee D Nelms, Levi Waldron, Luis A Barrera, Andrew W Weflen, Jeremy A Goettel, Guoji Guo, Robert K Montgomery, Marian R Neutra, David T Breault, Scott B Snapper, Stuart H Orkin, Martha L Bulyk, Curtis Huttenhower, Wayne I Lencer
We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our method, CellMapper, strongly outperforms previous computational algorithms to predict cell type-specific expression, especially for rare and difficult-to-isolate cell types. Furthermore, CellMapper makes accurate predictions for human brain cell types that have never been isolated, and can be rapidly applied to diverse cell types from many tissues...
September 29, 2016: Genome Biology
Ulrich Knief, Georg Hemmrich-Stanisak, Michael Wittig, Andre Franke, Simon C Griffith, Bart Kempenaers, Wolfgang Forstmeier
BACKGROUND: Inversion polymorphisms constitute an evolutionary puzzle: they should increase embryo mortality in heterokaryotypic individuals but still they are widespread in some taxa. Some insect species have evolved mechanisms to reduce the cost of embryo mortality but humans have not. In birds, a detailed analysis is missing although intraspecific inversion polymorphisms are regarded as common. In Australian zebra finches (Taeniopygia guttata), two polymorphic inversions are known cytogenetically and we set out to detect these two and potentially additional inversions using genomic tools and study their effects on embryo mortality and other fitness-related and morphological traits...
September 29, 2016: Genome Biology
Nina Koenecke, Jeff Johnston, Bjoern Gaertner, Malini Natarajan, Julia Zeitlinger
BACKGROUND: Drosophila dorso-ventral (DV) patterning is one of the best-understood regulatory networks to date, and illustrates the fundamental role of enhancers in controlling patterning, cell fate specification, and morphogenesis during development. Histone acetylation such as H3K27ac is an excellent marker for active enhancers, but it is challenging to obtain precise locations for enhancers as the highest levels of this modification flank the enhancer regions. How to best identify tissue-specific enhancers in a developmental system de novo with a minimal set of data is still unclear...
September 27, 2016: Genome Biology
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