Computational biology and bioinformatics

  • Article
    | Open Access

    TATA boxes in gene promoters are associated with high level of cell-to-cell variation in gene expression. Through integration of multiple data sets, the authors now provide insights into how the interactions of TBP with DNA and other proteins can lead to noisy expression.

    • Charles N. J. Ravarani
    • , Guilhem Chalancon
    •  & M. Madan Babu
  • Article
    | Open Access

    The influence of species conservation on food webs is less well understood than the effects of species loss. Here, the authors test several indices against optimal food web management and find no current metrics are reliably effective at identifying species conservation priorities.

    • E. McDonald-Madden
    • , R. Sabbadin
    •  & H. P. Possingham
  • Article
    | Open Access

    The clinical application of new sequencing techniques is expected to accelerate pathogen identification. Here, Bradley et al. present a clinician-friendly software package that uses sequencing data for quick and accurate prediction of antibiotic resistance profiles for S. aureus and M. tuberculosis.

    • Phelim Bradley
    • , N. Claire Gordon
    •  & Zamin Iqbal
  • Article
    | Open Access

    Availability of computing power can limit computational analysis of large genetic and genomic datasets. Here, Canela-Xandri, et al. describe a software called DISSECT that is capable of analyzing large-scale genetic data by distributing the work across thousands of networked computers.

    • Oriol Canela-Xandri
    • , Andy Law
    •  & Albert Tenesa
  • Article
    | Open Access

    Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

    • Tyler S. Alioto
    • , Ivo Buchhalter
    •  & Ivo G. Gut
  • Article
    | Open Access

    Single-cell RNA-sequencing (scRNA-seq) can be applied to dissect the kinetics of gene expression and patterns of allele-specific expression. Here, Kim et al.report a generative statistical model that can separate biological variability from technical noise by quantifying technical noise using external RNA spike-ins.

    • Jong Kyoung Kim
    • , Aleksandra A. Kolodziejczyk
    •  & John C. Marioni
  • Article
    | Open Access

    In chromatin endogenous cleavage (ChEC), micrococcal nuclease (MNase) is fused to a protein of interest and its cleavage is thus targeted to specific genomic loci in vivo. Here, the authors show that time-resolved ChEC-seq (high-throughput sequencing after ChEC) can detect DNA shape patterns regardless of motif strength.

    • Gabriel E. Zentner
    • , Sivakanthan Kasinathan
    •  & Steven Henikoff
  • Article
    | Open Access

    Das et al. present a novel Bayesian approach called expression Quantitative Trait enhancer Loci (eQTeL), which effectively integrates genetic and epigenetic information to identify combination of regulatory genomic variants underlying expression variance. Using various functional data, the authors show the variants identified by eQTeL are likely to be causal.

    • Avinash Das
    • , Michael Morley
    •  & Sridhar Hannenhalli
  • Article
    | Open Access

    Assessing functional impact of mutations in cancer on gene expression can improve our understanding of cancer biology and may identify potential therapeutic targets. Here, Ding et al. describe a novel statistical model named xseq for a systematic survey of how mutations impact transcriptome landscapes across 12 different tumour types.

    • Jiarui Ding
    • , Melissa K. McConechy
    •  & Sohrab P. Shah
  • Article
    | Open Access

    The biochemical pathways of central carbon metabolism are highly conserved across all domains of life. Here, Courtet al. use a computational approach to test all possible pathways of glycolysis and gluconeogenesis and find that the existing trunk pathways may represent a maximal flux solution selected for during evolution.

    • Steven J. Court
    • , Bartlomiej Waclaw
    •  & Rosalind J. Allen
  • Article
    | Open Access

    Comprehensive digital information on species distributions is crucial for research in ecology, evolution and conservation. Here, Meyer et al.find large gaps and biases in global vertebrate point records, especially in emerging economies, and identify key factors currently limiting information.

    • Carsten Meyer
    • , Holger Kreft
    •  & Walter Jetz
  • Article
    | Open Access

    Cell-to-cell communication relies upon interactions between secreted ligands and cell surface receptors. Here, Ramilowski et al.present a draft cell-to-cell communication network based on expression of ligand-receptor pairs in 144 different human cell types.

    • Jordan A. Ramilowski
    • , Tatyana Goldberg
    •  & Alistair R. R. Forrest
  • Article
    | Open Access

    TALE proteins are popular tools for genome engineering because they can recognize specific DNA sequences, however off-target effects are a routine problem. Here Rogers and Barrera et al. comprehensively map TALE–DNA interactions to develop a computational model to predict binding specificity.

    • Julia M. Rogers
    • , Luis A. Barrera
    •  & Martha L. Bulyk
  • Article
    | Open Access

    Adverse drug reactions are an important clinical problem. Here the authors combine information about drug-induced gene expression changes and genetic variability of patients with a genome-scale metabolic model to identify drug-induced changes in cellular metabolism that may be linked to drug side effects.

    • Daniel C. Zielinski
    • , Fabian V. Filipp
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    Proteins are sometimes implicated in separate and seemingly unrelated processes, so called moonlighting functions. Here the authors use bioinformatics tools to identify extreme multifunctional proteins and define a signature of extreme multifunctionality.

    • Charles E. Chapple
    • , Benoit Robisson
    •  & Christine Brun
  • Article
    | Open Access

    Planctomycetes appear to differ from all other bacteria in their cellular organization and their apparent lack of a peptidoglycan (PG) cell wall. Here Jeske et al. show that Planctomycetes do possess a typical PG cell wall and that their cellular architecture resembles that of Gram-negative bacteria.

    • Olga Jeske
    • , Margarete Schüler
    •  & Christian Jogler
  • Article |

    There is currently no consensus on how best to identify and delimit biogeographical regions. Here the authors develop a network-based approach incorporating complex presence–absence patterns that can successfully identify commonly recognized biogeographical regions, and apply it to two large-scale data sets of plants and amphibians.

    • Daril A. Vilhena
    •  & Alexandre Antonelli
  • Article
    | Open Access

    Cells constantly integrate information from multiple stimuli. By considering every possible means by which two stimuli can interact, Cappuccio et al. define 10 interaction modes and demonstrate their preferential use by dendritic cells responding to different combinations of microbial and host inflammatory cues.

    • Antonio Cappuccio
    • , Raphaël Zollinger
    •  & Vassili Soumelis
  • Article |

    Artifacts caused by whole-genome amplification bias are a recurrent challenge in single-cell sequencing analysis. Here, the authors develop statistical models and demonstrate an efficient strategy for controlling amplification errors by a joint analysis of single cell genomes.

    • Cheng-Zhong Zhang
    • , Viktor A. Adalsteinsson
    •  & J. Christopher Love
  • Article |

    Sequential segmentation in development is best described in vertebrates, where it relies on cell proliferation and shows regular periodicity. Here, the authors show that in the flour beetle segments are added with irregular rate and their elongation during periods of fast growth relies mostly on cell movements.

    • A. Nakamoto
    • , S. D. Hester
    •  & T. A. Williams
  • Article
    | Open Access

    The key regulators that allow transition from proliferative to invasive phenotype in melanoma cells have not been identified yet. The authors perform chromatin and transcriptome profiling followed by comprehensive bioinformatics analysis identifying new candidate regulators for two distinct cell states of melanoma.

    • Annelien Verfaillie
    • , Hana Imrichova
    •  & Stein Aerts
  • Article
    | Open Access

    Gradients of the secreted morphogen Sonic Hedgehog (Shh) pattern the neural tube in vertebrates. Cohen et al.quantify Shh signalling in developing mice, and by constructing a computational model of the process, identify mechanisms by which the dynamics of Shh signalling are regulated.

    • Michael Cohen
    • , Anna Kicheva
    •  & James Briscoe
  • Article |

    The evolutionary origin of Hippopotamidae, the family of hippos, is poorly understood. Here, the authors describe a new fossil from Kenya that unambiguously roots Hippopotamidae into the group that includes the first large terrestrial mammals to invade Africa, more than 30 million years ago.

    • Fabrice Lihoreau
    • , Jean-Renaud Boisserie
    •  & Stéphane Ducrocq
  • Article
    | Open Access

    The activity of sensory neurons can be correlated with perceptual decisions and this effect may provide insights into how sensory information is processed during perceptual tasks. Here the authors develop a network model of sensory and decision-making areas and propose that the dynamics across the network hierarchy explains the choice probabilities.

    • Klaus Wimmer
    • , Albert Compte
    •  & Jaime de la Rocha
  • Article
    | Open Access

    Motor learning is characterized by diverse cognitive processes, which lack a unified theoretical framework. Here, Takiyama et al.present a model demonstrating that motor learning is determined by prospective errors, which they test in a specially designed visuomotor adaptation task.

    • Ken Takiyama
    • , Masaya Hirashima
    •  & Daichi Nozaki
  • Article
    | Open Access

    Understanding the dynamics of enzyme-substrate complexation provides an insight into potential drugs, but intermediate states are difficult to observe experimentally. Here, the authors use simulations and machine learning to analyse the binding of transition state inhibitors to purine nucleoside phosphorylase.

    • Sergio Decherchi
    • , Anna Berteotti
    •  & Andrea Cavalli
  • Article
    | Open Access

    Understanding the epidemiology of malaria transmission between humans and mosquitoes is crucial for successful disease control. Analysing data from an 18-year malaria control programme, Churcher et al. show that decreased parasite prevalence in humans can be found concurrently with an increase in transmission efficiency.

    • Thomas S. Churcher
    • , Jean-François Trape
    •  & Anna Cohuet
  • Article |

    Body plan complexity is associated with the number of different cell types, yet the processes that create this diversity are unclear. Here the authors use transcriptomics to test the hypothesis that unlike cancer cells, novel normal cell types arise through sub-specialization of an ancestral cell type.

    • Cong Liang
    • , Alistair R.R. Forrest
    •  & Günter P. Wagner
  • Article |

    The structure of insect odorant receptors (ORs) has remained elusive due to their lack of homology to other proteins and the inability to obtain OR crystals. Here, the authors use amino acid evolutionary covariation patterns to fold these proteins de novoand generate the first three-dimensional models of insect ORs.

    • Thomas A. Hopf
    • , Satoshi Morinaga
    •  & Richard Benton
  • Article
    | Open Access

    Cellular imaging studies can generate large volumes of complex phenotypic data; however, presenting this information in a form that quickly conveys trends in the data set remains a challenge. Sailem et al.present a tool which translates such data into easily interpretable cell-like glyphs.

    • Heba Z. Sailem
    • , Julia E. Sero
    •  & Chris Bakal
  • Article
    | Open Access

    The correct assembly of genomes from sequencing data remains a challenge due to difficulties in correctly assigning the location of repeated DNA elements. Here the authors describe GRAAL, an algorithm that utilizes genome-wide chromosome contact data within a probabilistic framework to produce accurate genome assemblies.

    • Hervé Marie-Nelly
    • , Martial Marbouty
    •  & Romain Koszul
  • Article |

    microRNAs are short non-coding RNAs that post-transcriptionally regulate gene expression for which the identification of promoter and primary transcripts (pri-miRNAs) has been difficult. Here the authors describe microTSS, an algorithm that supports the precise identification of intergenic pri-miRNA transcription start sites.

    • Georgios Georgakilas
    • , Ioannis S. Vlachos
    •  & Artemis G. Hatzigeorgiou
  • Article |

    Metabolites produced by the gut microbiota can potentially affect our physiology. Here, the authors present a metabolomics strategy that models microbiota metabolism as a reaction network and uses pathway analysis to facilitate identification and characterization of microbial metabolites.

    • Gautham V. Sridharan
    • , Kyungoh Choi
    •  & Arul Jayaraman
  • Article |

    A large portion of the transcribed genome—such as introns and noncoding RNAs—is believed to not be translated into protein products. Here, the authors provide evidence for the existence of regulated peptide products that are translated from transcribed sequences generally characterized as noncoding.

    • Sudhakaran Prabakaran
    • , Martin Hemberg
    •  & Judith A. Steen
  • Article
    | Open Access

    CpG islands are high GC content DNA elements that surround the majority of transcriptional start sites in eukaryotes. Here, the authors analyse over 200 genomic data sets to provide new insight into global CpG islands-dependent regulatory mechanisms in differentiated and pluripotent stem cells.

    • Samuel Beck
    • , Bum-Kyu Lee
    •  & Jonghwan Kim
  • Article |

    Despite our growing understanding of their complexity, different types of RNA are still classified using technical rather than functional criteria. Andersson et al.show that categorization of RNAs based on stability and direction of transcription is an effective means of functional classification.

    • Robin Andersson
    • , Peter Refsing Andersen
    •  & Albin Sandelin
  • Article |

    The development of software tools to analyse large mass spectrometry data sets lags behind the increase in diversity of the data. Here the authors develop MS-GF+, a database search tool that outperforms other popular tools in identifying peptides from a variety of data sets.

    • Sangtae Kim
    •  & Pavel A. Pevzner
  • Article
    | Open Access

    No experimental evidence exists for intra-helical motion of DNA at the μs timescale, which has been attributed to technical difficulties in observing motion in this time range. Here, the authors demonstrate, using extensive molecular dynamics simulations and experimental analysis, that such motion is effectively absent from a B-DNA duplex.

    • Rodrigo Galindo-Murillo
    • , Daniel R. Roe
    •  & Thomas E. Cheatham III
  • Article
    | Open Access

    Metastasizing tumour cells undergo epithelial-to-mesenchymal transition. Using both bioinformatic and in vivo approaches, Chanrion et al.identify combined Notch activation and p53 inactivation as a potent inducer of this transition, and apply this to create a highly metastatic tumour model in mice.

    • Maia Chanrion
    • , Inna Kuperstein
    •  & Sylvie Robine
  • Article
    | Open Access

    Linear mixed models (LMMs) provide a powerful method for studying genotype–phenotype associations. Here the authors present a LMM application that estimates an optimal transformation from observed data and increases the accuracy of heritability estimation and phenotype prediction.

    • Nicolo Fusi
    • , Christoph Lippert
    •  & Oliver Stegle