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| Open AccessEstimation of immune cell content in tumour tissue using single-cell RNA-seq data
Mathematical approaches can be used to assess immune cell composition from the tumour's bulk expression data. Here the authors optimise the CYBERSORT-based deconvolution algorithm by including cell type-specific reference gene expression profiles generated from tumour-derived single-cell RNA sequencing data.
- Max Schelker
- , Sonia Feau
- & Andreas Raue
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Article
| Open AccessDifferentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing
There is a need to understand how mammary epithelial cells respond to changes at various developmental stages. Here, the authors use single-cell RNA sequencing of mammary epithelial cells at different adult developmental stages, identifying different cell types and charting their developmental trajectory.
- Karsten Bach
- , Sara Pensa
- & Walid T. Khaled
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Article
| Open AccessIntegrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions
Rising rates of peanut allergy pose a public health problem. Here, the authors profile blood transcriptomes during double-blind, placebo-controlled oral challenge in peanut-allergic children to identify gene and cell composition changes, and construct causal networks to detect key allergic reaction drivers.
- C. T. Watson
- , A. T. Cohain
- & S. Bunyavanich
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Article
| Open AccessMeta-analysis of gut microbiome studies identifies disease-specific and shared responses
Reported associations between the human microbiome and disease are often inconsistent. Here, Duvallet et al. perform a meta-analysis of 28 gut microbiome studies spanning ten diseases, and find associations that are likely not disease-specific but potentially part of a shared response to disease.
- Claire Duvallet
- , Sean M. Gibbons
- & Eric J. Alm
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Article
| Open AccessNetwork dynamics-based cancer panel stratification for systemic prediction of anticancer drug response
Genomic alterations underlie the variability of drug responses between cancers, but our mechanistic understanding is limited. Here the authors use the p53 network to study how rewiring of signalling networks by genomic alterations impact their dynamic response to pharmacological perturbation.
- Minsoo Choi
- , Jue Shi
- & Kwang-Hyun Cho
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Article
| Open AccessInference of differentiation time for single cell transcriptomes using cell population reference data
Single cell transcriptome data can be used to determine developmental lineage trajectories. Here the authors map single cell transcriptomes onto a differentiation trajectory defined by cell population transcriptomes and show that cell cycle regulators have a role in differentiation timing.
- Na Sun
- , Xiaoming Yu
- & Jing-Dong J. Han
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Article
| Open AccessCentromere evolution and CpG methylation during vertebrate speciation
Centromeres and large-scale structural variants evolve and contribute to genome diversity during vertebrate speciation. Here Ichikawa et al perform de novo long-read genome assembly of three inbred medaka strains, and report long-range structure of centromeres and their methylation as well as correlation of structural variants with differential gene expression.
- Kazuki Ichikawa
- , Shingo Tomioka
- & Shinich Morishita
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Article
| Open AccessFunctional mapping and annotation of genetic associations with FUMA
Prioritizing genetic variants is a major challenge in genome-wide association studies. Here, the authors develop FUMA, a web-based bioinformatics tool that uses a combination of positional, eQTL and chromatin interaction mapping to prioritize likely causal variants and genes.
- Kyoko Watanabe
- , Erdogan Taskesen
- & Danielle Posthuma
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Article
| Open AccessNSD1- and NSD2-damaging mutations define a subset of laryngeal tumors with favorable prognosis
The authors use an integrative clustering approach to identify two laryngeal cancer clusters with distinct prognosis and show that mutations damaging the NSD1 and NSD2 methyltransferases segregate to the cluster with favorable prognosis, and independently predict longer survival in patients with laryngeal, but not other head and neck cancers.
- Suraj Peri
- , Evgeny Izumchenko
- & Erica A. Golemis
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Article
| Open AccessSingle-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions
Eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that exist at the kilo-megabase scale. Here Cattoni et al. combine super-resolution microscopy with DNA-labeling methods to quantify absolute frequencies of interactions within TADs.
- Diego I. Cattoni
- , Andrés M. Cardozo Gizzi
- & Marcelo Nollmann
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Article
| Open AccessVisual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types
Single cell profiling yields high dimensional data of very large numbers of cells, posing challenges of visualization and analysis. Here the authors introduce a method for analysis of mass cytometry data that can handle very large datasets and allows their intuitive and hierarchical exploration.
- Vincent van Unen
- , Thomas Höllt
- & Boudewijn P. F. Lelieveldt
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Article
| Open AccessGenome-wide identification and differential analysis of translational initiation
Translation initiation sequencing (TI-seq) has revealed unexpected diversity in protein isoforms. Here, Zhang et al. present Ribo-TISH, a computational toolkit that can detect and compare TIs across conditions and improve open reading frame prediction from different types of ribosome profiling data.
- Peng Zhang
- , Dandan He
- & Yiwen Chen
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Article
| Open AccessAn extracellular matrix-related prognostic and predictive indicator for early-stage non-small cell lung cancer
Prognosis and prediction of adjuvant chemotherapy response in non-small cell lung cancer can have significant clinical impact. Here, the authors show that differential expression of a 29 extracellular matrix gene indicator, EPPI, can predict patient outcome.
- Su Bin LIM
- , Swee Jin TAN
- & Chwee Teck LIM
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Article
| Open AccessExocytosis-coordinated mechanisms for tip growth underlie pollen tube growth guidance
Tip-growing cells can find their growing path toward the source of attractive signals. Here, using experimental data and mathematical modeling, Luo et al. demonstrate that tip-localized exocytosis can integrate guidance cues with Rho GTPase signaling to control cell wall mechanics and direct tip growth in Arabidopsis pollen tubes.
- Nan Luo
- , An Yan
- & Zhenbiao Yang
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Article
| Open AccessDeconvoluting interrelationships between concentrations and chemical shifts in urine provides a powerful analysis tool
The NMR chemical shifts of a substance in urine strongly depend on the composition of the mixture itself, and this makes automatic assignment for quantification very difficult. Here the authors show the chemical shifts of signals and the concentration of NMR-invisible inorganic ions in urine, are predictable.
- Panteleimon G. Takis
- , Hartmut Schäfer
- & Claudio Luchinat
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Article
| Open AccessDecoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition
The role of lncRNA is unclear with respect to epithelial-to-mesenchymal transition (EMT), which is linked to ovarian cancer metastasis. Here, the authors show lncRNA DNM3OS expression contributes to ovarian cancer EMT, cell migration/invasion, and correlates with worse overall patient survival.
- Ramkrishna Mitra
- , Xi Chen
- & Christine M. Eischen
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Article
| Open AccessShaping bacterial population behavior through computer-interfaced control of individual cells
Individual bacteria interact with each other and their environment to produce population-level patterns of gene expression. Here the authors use an automated platform combined with optogenetic feedback to manipulate population behaviors through dynamic control of individual cells.
- Remy Chait
- , Jakob Ruess
- & Călin C. Guet
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Article
| Open AccessComparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations
Esophageal squamous cell carcinoma (ESCC) exhibits differences in incidence and survival patterns among races. Here, analysis of Chinese and TCGA ESCC patients reveals that Asian patients exhibit higher TP53, EP300 and NFE2L2 mutational frequencies, and mutated CSMD3 associates with better prognosis.
- Jiaying Deng
- , Hu Chen
- & Kuaile Zhao
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Article
| Open AccessA comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
The NUDIX hydrolases are known to be involved in several cellular processes and diseases, such as cancer, but remain poorly characterized as a family. Here, the authors provide a comprehensive analysis of the structural, biochemical, and expression properties of 18 human NUDIX proteins, and begin to address their functional inter-relationships.
- Jordi Carreras-Puigvert
- , Marinka Zitnik
- & Thomas Helleday
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Article
| Open AccessGenome-driven evolutionary game theory helps understand the rise of metabolic interdependencies in microbial communities
The rise of metabolic interdependencies among microbes is still poorly understood. Here, taking the underlying biochemical networks into consideration, Zomorrodi and Segrè integrate genome-scale metabolic models with evolutionary game theory to study the rise of cross-feeding in microbial communities.
- Ali R. Zomorrodi
- & Daniel Segrè
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Article
| Open AccessSignificance estimation for large scale metabolomics annotations by spectral matching
Matching fragment spectra to reference library spectra is an important procedure for annotating small molecules in untargeted mass spectrometry based metabolomics studies. Here, the authors develop strategies to estimate false discovery rates (FDR) by empirical Bayes and target-decoy based methods which enable a user to define the scoring criteria for spectral matching.
- Kerstin Scheubert
- , Franziska Hufsky
- & Sebastian Böcker
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Article
| Open AccessNetwork inference from glycoproteomics data reveals new reactions in the IgG glycosylation pathway
IgG glycosylation is an important factor in immune function, yet the molecular details of protein glycosylation remain poorly understood. The data-driven approach presented here uses large-scale plasma IgG mass spectrometry measurements to infer new biochemical reactions in the glycosylation pathway.
- Elisa Benedetti
- , Maja Pučić-Baković
- & Jan Krumsiek
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Article
| Open AccessRNA editing by ADAR1 leads to context-dependent transcriptome-wide changes in RNA secondary structure
Adenosine deaminase acting on RNA 1 (ADAR1) edits adenosine to inosine. Here the authors, using parallel analysis of RNA secondary structure sequencing, provide evidence that ADAR1 induces sequence-context-dependent RNA secondary structures changes, often leading to stabilization of the RNA duplex.
- Oz Solomon
- , Ayelet Di Segni
- & Gidi Rechavi
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Article
| Open AccessOrigin of the omnipotence of eukaryotic release factor 1
The eukaryotic release factor eRF1 is able to recognize the three stop codons UAA, UAG and UGA with high accuracy, while discriminating against near-cognate codons. Here the authors use molecular dynamic simulation to provide insight into the molecular basis behind the remarkable codon specificity of eRF1.
- Christoffer Lind
- , Ana Oliveira
- & Johan Åqvist
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Article
| Open AccessThe North American bullfrog draft genome provides insight into hormonal regulation of long noncoding RNA
The globally-distributed Ranidae (true frogs) are the largest frog family. Here, Hammond et al. present a draft genome of the North American bullfrog, Rana (Lithobates) catesbeiana, as a foundation for future understanding of true frog genetics as amphibian species face difficult environmental challenges.
- S. Austin Hammond
- , René L. Warren
- & Inanc Birol
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Article
| Open AccessAssessing the impact of imperfect adherence to artemether-lumefantrine on malaria treatment outcomes using within-host modelling
Artemether lumefantrine is widely used for the treatment of uncomplicated malaria. The impact of imperfect patient adherence to the six-dose regimen is hard to assess. Using adherence data for unsupervised patients, the authors model how suboptimal adherence affects treatment outcomes.
- Joseph D. Challenger
- , Katia Bruxvoort
- & Lucy C. Okell
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Article
| Open AccessParadoxes in leaky microbial trade
Microbes live in communities and exchange metabolites, but the resulting dynamics are poorly understood. Here, the authors study the interplay between metabolite production strategies and population dynamics, and find that complex and unexpected dynamics emerge even in simple microbial economies.
- Yoav Kallus
- , John H. Miller
- & Eric Libby
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Article
| Open AccessThe challenge of mapping the human connectome based on diffusion tractography
Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.
- Klaus H. Maier-Hein
- , Peter F. Neher
- & Maxime Descoteaux
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Article
| Open AccessMutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis
Tumorigenesis is a complex process driven by numerous risk factors. Here, genomic analysis of liver cancer reveals the evolution of mutational signatures during tumor development, highlighting mutational and structural signatures linked to environmental exposures and endogenous cellular processes.
- Eric Letouzé
- , Jayendra Shinde
- & Jessica Zucman-Rossi
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Article
| Open AccessDense and accurate whole-chromosome haplotyping of individual genomes
Haplotype information is important in investigating many biological phenomena. Here, Porubsky et al. combine Strand-seq with long-read or linked-read sequencing to obtain complete and genome-wide haplotypes of a single individual genome at manageable costs.
- David Porubsky
- , Shilpa Garg
- & Tobias Marschall
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Article
| Open AccessStructure-mediated modulation of mRNA abundance by A-to-I editing
RNA A-to-I editing introduces single nucleotide changes to RNA, but its role in cells remains unclear. Here, the authors analyse A-to-I editomes in human samples and find that A-to-I editing stabilizes RNA secondary structures and reduces the accessibility of AGO2-miRNA to target sites in mRNAs.
- Anneke Brümmer
- , Yun Yang
- & Xinshu Xiao
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Article
| Open AccessPercolation transition of cooperative mutational effects in colorectal tumorigenesis
Cancer is caused by accumulating genetic mutations. Here, the authors investigate the cooperative effect of these mutations in colorectal cancer patients and identify a giant cluster of mutation-propagating modules that undergoes percolation transition during tumorigenesis.
- Dongkwan Shin
- , Jonghoon Lee
- & Kwang-Hyun Cho
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Article
| Open AccessIdentifying host regulators and inhibitors of liver stage malaria infection using kinase activity profiles
Host kinases facilitate Plasmodium liver stage (LS) infection, but systematic accounting of important players is lacking. Here, the authors use a computational approach and kinase activity profiles to identify host kinase regulators of LS infection and drugs that could eliminate parasite burden.
- Nadia Arang
- , Heather S. Kain
- & Alexis Kaushansky
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Article
| Open AccessPan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors
Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, the authors conduct pan-cancer analyses and apply statistical modelling to identify 27 candidate tumour suppressors, including MAFTRR, KIAA1551, and IGF2BP2.
- Jiqiu Cheng
- , Jonas Demeulemeester
- & Peter Van Loo
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Article
| Open AccessAlgorithm for post-clustering curation of DNA amplicon data yields reliable biodiversity estimates
A central problem in biodiversity estimation from genetic markers is the ability of algorithms to retain ‘true’ species while discarding artefacts. Here, the authors present a new post-clusturing curation algorithm using OTU co-occurrences to estimate plant biodiversity from soil samples.
- Tobias Guldberg Frøslev
- , Rasmus Kjøller
- & Anders Johannes Hansen
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Article
| Open AccessPLATO software provides analytic framework for investigating complexity beyond genome-wide association studies
Centralized infrastructure to support analyses involving complexity beyond genome-wide association studies is broadly needed. Here, Ritchie and colleagues develop PLATO, a software tool to process and integrate various methods for this task.
- Molly A. Hall
- , John Wallace
- & Marylyn D. Ritchie
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Article
| Open AccessFunctional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation cascade from an uncultured archaeon
In eukaryotic cells, the ubiquitylation system regulates several cellular processes central to protein homoeostasis. Here the authors demonstrate the existence of an eukaryotic-like ubiquitylation cascade requiring E1, E2 and E3-like enzymes in the archaeon C. subterraneum, shedding light on the evolution of the ubiquitin-proteasome system.
- Rory Hennell James
- , Eva F. Caceres
- & Nicholas P. Robinson
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Article
| Open AccessGene isoforms as expression-based biomarkers predictive of drug response in vitro
Altered mRNA splicing features in many cancers, but it has not been linked to drug response. Here, with their meta-analytic framework, the authors analyse pharmacogenomic data to identify isoform-based biomarkers predictive of in vitro drug response, and show them to frequently be strong predictors.
- Zhaleh Safikhani
- , Petr Smirnov
- & Benjamin Haibe-Kains
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Article
| Open AccessComprehensive analysis of normal adjacent to tumor transcriptomes
Normal tissue adjacent to the tumour (NAT) is often used as a control in cancer studies. Here, the authors analyse across cancer types the transcriptomes of healthy, NAT, and tumour tissues, and find that NAT presents a unique state, potentially due to inflammatory response of the NAT to the tumour tissue.
- Dvir Aran
- , Roman Camarda
- & Atul J. Butte
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Article
| Open AccessAn integrative method to decode regulatory logics in gene transcription
Existing transcriptional regulatory networks models fall short of deciphering the cooperation between multiple transcription factors on dynamic gene expression. Here the authors develop an integrative method that combines gene expression and transcription factor-DNA binding data to decode transcription regulatory logics.
- Bin Yan
- , Daogang Guan
- & Hailong Zhu
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Article
| Open AccessThe β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
Binding of viral envelope glycoproteins (Env) to the host cell CD4 receptor mediates HIV-1 entry. Here, the authors develop compounds that inhibit the CD4-induced conformational changes in Env and show that the gp120 β20-β21 element is a key regulator for Env transitions.
- Alon Herschhorn
- , Christopher Gu
- & Joseph G. Sodroski
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Article
| Open AccessGenome-wide prediction of DNase I hypersensitivity using gene expression
A map of the activities of all genomic regulatory elements across cell types and conditions would be a tremendous resource. The computational method introduced here predicts genome-wide accessible sites from gene expression data and allows the authors to build a database of regulatory element activities using publicly available transcriptome data.
- Weiqiang Zhou
- , Ben Sherwood
- & Hongkai Ji
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Article
| Open AccessWind loads and competition for light sculpt trees into self-similar structures
Tree branches follow allometric scalings between length, thickness and dry mass. Here, Eloy and colleagues develop a functional-structural model that shows how such allometries in tree architecture can emerge through evolution as a result of competition for light, wind biomechanics, and wind sensing.
- Christophe Eloy
- , Meriem Fournier
- & Bruno Moulia
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Article
| Open AccessInference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer’s disease
“mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer’s disease.”
- Rached Alkallas
- , Lisa Fish
- & Hamed S. Najafabadi
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Article
| Open AccessCounteracting structural errors in ensemble forecast of influenza outbreaks
Inaccuracy of influenza forecasts based on dynamical models is partly due to nonlinear error growth. Here the authors address the error structure of a compartmental influenza model, and develop a new improved forecast approach combining dynamical error correction and statistical filtering techniques.
- Sen Pei
- & Jeffrey Shaman
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Article
| Open AccessPan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes
Germline mutations in homologous recombination (HR) DNA repair genes are linked to breast and ovarian cancer. Here, the authors show that mutually exclusive bi-allelic inactivation of HR genes are present in other cancer types and associated with genomic features of HR deficiency, expanding the potential use of HR-directed therapies.
- Nadeem Riaz
- , Pedro Blecua
- & Jorge S. Reis-Filho
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Article
| Open AccessIntegrative analysis of genomic and epigenomic regulation of the transcriptome in liver cancer
Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.
- Hyun Goo Woo
- , Ji-Hye Choi
- & Yoon Jun Kim
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Article
| Open AccessThe chromosomal organization of horizontal gene transfer in bacteria
Horizontal gene transfer (HGT) is an important mechanism for genome evolution and adaptation in bacteria. Here, Oliveira and colleagues find HGT hotspots comprising ~ 1% of the chromosomal regions in 80 bacterial species.
- Pedro H. Oliveira
- , Marie Touchon
- & Eduardo P. C. Rocha
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Article
| Open AccessCNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.
- Aurélien Macé
- , Marcus A. Tuke
- & Zoltán Kutalik
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