bluuebunny/crossref_metadata_2025 huggingface dataset:
DoubletDecon: Cell-State Aware Removal of Single-Cell RNA-Seq Doublets
Authors: DePasquale Erica A.K. , Schnell Daniel J. , Valiente-Alandí Íñigo , Blaxall Burns C. , Grimes H. Leighton , Singh Harinder , Salomonis Nathan
Published: July 2018

Methods for single-cell RNA sequencing (scRNA-Seq) have greatly advanced in recent years. While droplet- and well-based methods have increased the capture frequency of cells for scRNA-Seq, these technologies readily produce technical artifacts, such as doublet-cell and multiplet-cell captures. Doublets occurring between distinct cell-types can appear as hybrid scRNA-Seq profiles, but do not have distinct transcriptomes from individual cell states. We introduce DoubletDecon, an approach that detects doublets with a combination of deconvolution analyses and the identification of unique cell-state gene expression. We demonstrate the ability of DoubletDecon to identify synthetic and cell-hashing cell singlets and doublets from scRNA-Seq datasets of varying cellular complexity. DoubletDecon is able to account for cell-cycle effects and is compatible with diverse species and unsupervised population detection algorithms (e.g., ICGS, Seurat). We believe this approach has the potential to become a standard quality control step for the accurate delineation of cell states.
Accurate Prediction of Antibody Resistance in Clinical HIV-1 Isolates
Authors: Rawi Reda , Mall Raghvendra , Shen Chen-Hsiang , Doria-Rose Nicole A. , Farney S. Katie , Shiakolas Andrea , Zhou Jing , Chun Tae-Wook , Lynch Rebecca M. , Mascola John R. , Kwong Peter D. , Chuang Gwo-Yu
Published: July 2018

Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection with several undergoing clinical trials. Due to high sequence diversity and mutation rate of HIV-1, viral isolates are often resistant to particular bNAbs. Resistant strains are commonly identified by time-consuming and expensive in vitro neutralization experiments. Here, we developed machine learning-based classifiers that accurately predict resistance of HIV-1 strains to 33 neutralizing antibodies. Notably, our classifiers achieved an overall prediction accuracy of 96% for 212 clinical isolates from patients enrolled in four different clinical trials. Moreover, use of the tree-based machine learning method gradient boosting machine enabled us to identify critical epitope features that distinguish between antibody resistance and sensitivity. The availability of an in silico antibody resistance predictor will facilitate informed decisions of antibody usage in clinical settings.
Repeated evolution of asexuality involves convergent gene expression changes
Authors: Parker Darren J. , Bast Jens , Jalvingh Kirsten , Dumas Zoé , Robinson-Rechavi Marc , Schwander Tanja
Published: July 2018

Asexual reproduction has evolved repeatedly from sexual ancestors across a wide range of taxa. While the costs and benefits associated with asexuality have received considerable attention, the molecular changes underpinning the evolution of asexual reproduction remain relatively unexplored. In particular, it is completely unknown whether the repeated evolution of asexual phenotypes involves similar molecular changes, as previous studies have focused on changes occurring in single lineages. Here we investigate the extent of convergent gene expression changes across five independent transitions to asexuality in stick insects. We compared gene expression of asexual females to females of close sexual relatives in whole-bodies, reproductive tracts, and legs. We identified a striking amount of convergent gene expression change (up to 8% of genes), greatly exceeding that expected by chance. Convergent changes were also tissue-specific, and most likely driven by selection for functional changes. Genes showing convergent changes in the reproductive tract were associated with meiotic spindle formation and centrosome organization. These genes are particularly interesting as they can influence the production of unreduced eggs, a key barrier to asexual reproduction. Changes in legs and whole-bodies were likely involved in female sexual trait decay, with enrichment in terms such as sperm-storage and pigmentation. By identifying changes occurring across multiple independent transitions to asexuality, our results provide a rare insight into the molecular basis of asexual phenotypes and suggest that the evolutionary path to asexuality is highly constrained, requiring repeated changes to the same key genes.
Pseudomonas aeruginosainhibitsRhizopus microsporusgermination through sequestration of free environmental iron
Authors: Kousser Courtney , Clark Callum , Voelz Kerstin , Hall Rebecca A.
Published: July 2018

Rhizopus sppare the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infection. Key to pathogenesis is the ability of fungal spores to swell, germinate, and penetrate surrounding tissues. Antibiotic treatment in at-risk patients increases the probability of the patient developing mucormycosis, suggesting that bacteria have the potential to control the growth of the fungus. However, research into polymicrobial relationships involvingRhizopus spphas not been extensively explored. Here we show that co-culturingRhizopus microsporusandPseudomonas aeruginosaresults in the inhibition of spore germination. This inhibition was mediated via the secretion of bacterial siderophores, confirming the essential role of iron for fungal growth. Addition ofP. aeruginosasiderophores toR. microsporusspores in the zebrafish larval model of infection resulted in inhibition of fungal germination and reduced host mortality. Therefore, during infection antibacterial treatment may relieve bacterial imposed nutrient restriction resulting in secondary fungal infections.
Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape
Authors: Froberg John E. , Pinter Stefan F. , Kriz Andrea J. , Jégu Teddy , Lee Jeannie T.
Published: July 2018

The mammalian inactive X-chromosome (Xi) is structurally distinct from all other chromosomes and serves as a model for how the 3D genome is organized. The Xi shows weakened topologically associated domains and is instead organized into megadomains and superloops directed by the noncoding loci, Dxz4 and Firre. Their functional significance is presently unclear, though one study suggests that they permit Xi genes to escape silencing. Here, we find that megadomains do not precede Xist expression or Xi gene silencing. Deleting Dxz4 disrupts megadomain formation, whereas deleting Firre weakens intra-megadomain interactions. Surprisingly, however, deleting Dxz4 and Firre has no impact on Xi silencing and gene escape. Nor does it affect Xi nuclear localization, stability, or H3K27 methylation. Additionally, ectopic integration of Dxz4 and Xist is not sufficient to form megadomains on autosomes, further uncoupling megadomain formation from chromosomal silencing. We conclude that Dxz4 and megadomains are dispensable for Xi silencing and escape from X-inactivation.
Differential screening identifies molecules specifically inhibiting CCR5 transport to the cell surface and HIV infection
Authors: Boncompain Gaelle , Herit Floriane , Tessier Sarah , Lescure Aurianne , Del Nery Elaine , Gestraud Pierre , Staropoli Isabelle , Fukata Yuko , Fukata Masaki , Brelot Anne , Niedergang Florence , Perez Franck
Published: July 2018

Proteins destined to the cell surface are conveyed through membrane-bound compartments using the secretory pathway. Multiple secretory routes exist in cells, which paves the way to the development of inhibitory molecules able to specifically perturb the transport of a chosen cargo. We used differential high-content screening of chemical libraries to identify molecules reducing the secretion of CCR5, the major co-receptor for HIV-1 entry. Three molecules strongly affected the anterograde transport of CCR5, without inhibiting the transport of the related G protein-coupled receptors CCR1 and CXCR4. These three molecules perturb the transport of endogenous CCR5 and decrease the entry of HIV in human primary target cells. Two molecules were found to share the same mode of action, inhibiting palmitoylation of CCR5. Our results demonstrate that secretory routes can be specifically targeted which allows to envisage novel strategies to provoke the intracellular retention or rerouting of secretory proteins involved in disease development.
Single-cell isoform RNA sequencing (ScISOr-Seq) across thousands of cells reveals isoforms of cerebellar cell types
Authors: Gupta Ishaan , Collier Paul G , Haase Bettina , Mahfouz Ahmed , Joglekar Anoushka , Floyd Taylor , Koopmans Frank , Barres Ben , Smit August B , Sloan Steven , Luo Wenjie , Fedrigo Olivier , Ross M Elizabeth , Tilgner Hagen U
Published: July 2018

Full-length isoform sequencing has advanced our knowledge of isoform biology1–11. However, apart from applying full-length isoform sequencing to very few single cells12,13, isoform sequencing has been limited to bulk tissue, cell lines, or sorted cells. Single splicing events have been described for <=200 single cells with great statistical success14,15, but these methods do not describe full-length mRNAs. Single cell short-read 3’ sequencing has allowed identification of many cell sub-types16–23, but full-length isoforms for these cell types have not been profiled. Using our new method of single-cell-isoform-RNA-sequencing (ScISOr-Seq) we determine isoform-expression in thousands of individual cells from a heterogeneous bulk tissue (cerebellum), without specific antibody-fluorescence activated cell sorting. We elucidate isoform usage in high-level cell types such as neurons, astrocytes and microglia and finer sub-types, such as Purkinje cells and Granule cells, including the combination patterns of distant splice sites6–9,24,25, which for individual molecules requires long reads. We produce an enhanced genome annotation revealing cell-type specific expression of known and 16,872 novel (with respect to mouse Gencode version 10) isoforms (see isoformatlas.com).

ScISOr-Seq describes isoforms from >1,000 single cells from bulk tissue without cell sorting by leveraging two technologies in three steps: In step one, we employ microfluidics to produce amplified full-length cDNAs barcoded for their cell of origin. This cDNA is split into two pools: one pool for 3’ sequencing to measure gene expression (step 2) and another pool for long-read sequencing and isoform expression (step 3). In step two, short-read 3’-sequencing provides molecular counts for each gene and cell, which allows clustering cells and assigning a cell type using cell-type specific markers. In step three, an aliquot of the same cDNAs (each barcoded for the individual cell of origin) is sequenced using Pacific Biosciences (“PacBio”)1,2,4,5,26 or Oxford Nanopore3. Since these long reads carry the single-cell barcodes identified in step two, one can determine the individual cell from which each long read originates. Since most single cells are assigned to a named cluster, we can also assign the cell’s cluster name (e.g. “Purkinje cell” or “astrocyte”) to the long read in question (Fig 1A) – without losing the cell of origin of each long read.
Extracellular histones, a new class of inhibitory molecules of CNS axonal regeneration
Authors: Siddiq Mustafa M. , Hannila Sari S. , Zorina Yana , Nikulina Elena , Rabinovich Vera , Hou Jianwei , Huq Rumana , Richman Erica L. , Tolentino Rosa E. , Hansen Jens , Velenosi Adam , Kwon Brian K. , Tsirka Stella E. , Maze Ian , Sebra Robert , Iyengar Ravi , Filbin Marie T.
Published: July 2018

Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking the major myelin-associated inhibitors do not display spontaneous regeneration after injury, indicating the presence of other inhibitors. Searching for such inhibitors we have detected elevated levels of histone H3 in human cerebrospinal fluid (CSF) 24 hours after spinal cord injury. Following dorsal column lesions in mice and optic nerve crushes in rats, elevated levels of extracellular histone H3 were detected at the injury site. Similar to myelin-associated inhibitors, these extracellular histones induced growth cone collapse and inhibited neurite outgrowth. Histones mediate inhibition through the transcription factor YB-1 and Toll-like receptor 2, and these effects are independent of the Nogo receptor. Histone-mediated inhibition can be reversed by the addition of activated protein C (APC) in vitro, and APC treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS.

One sentence summary

Proteins typically associated with chromatin structure play an unexpected role in limiting axonal regeneration after injury.
QTL mapping and identification of corresponding genomic regions for black pod disease resistance to threePhytophthoraspecies inTheobroma cacaoL
Authors: Barreto MA , Rosa JRBF , Holanda ISA , Cardoso-Silva CB , Vildoso CIA , Ahnert D , Souza MM , Corrêa RX , Royaert S , Marelli J , Santos ESL , Luz EDMN , Garcia AAF , Souza AP
Published: July 2018

The cacao tree (Theobroma cacaoL.) is a species of great importance because cacao beans are the raw material used in the production of chocolate. However, the economic success of cacao is largely limited by important diseases such as black pod, which is responsible for losses of up to 30-40% of the global cacao harvest. The discovery of resistance genes could extensively reduce these losses. Therefore, the aims of this study were to construct an integrated multipoint genetic map, align polymorphisms against the available cacao genome, and identify quantitative trait loci (QTLs) associated with resistance to black pod disease in cacao. The genetic map had a total length of 956.41 cM and included 186 simple sequence repeat (SSR) markers distributed among 10 linkage groups. The physical “in silico” map covered more than 200 Mb of the cacao genome. Based on the mixed model predicted means ofPhytophthoraevaluation, a total of 6 QTLs were detected forPhytophthora palmivora(1 QTL),Phytophthora citrophthora(1 QTL), andPhytophthora capsici(4 QTLs). Approximately 1.77% to 3.29% of the phenotypic variation could be explained by the mapped QTLs. Several SSR marker-flanking regions containing mapped QTLs were located in proximity to disease regions. The greatest number of resistance genes was detected in linkage group 6, which provides strong evidence for a QTL. This joint analysis involving multipoint and mixed-model approaches may provide a potentially promising technique for detecting genes resistant to black pod and could be very useful for future studies in cacao breeding.
Uric acid lowering treatment alleviates perivascular carotid collar placement induced neointimal lesions in Uricase knockout mice
Authors: Lu Jie , Sun Ming-Shu , Wu Xin-Jiang , Yuan Xuan , Liu Zhen , Qu Xiao-Jie , Ji Xiao-Peng , Merriman Tony R , Li Chang-Gui
Published: July 2018

Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate on atherosclerosis development remains elusive. We aimed to use a new HU mouse model (Uricase/Uox knockout (KO)) to further investigate the relationship between HU and atherosclerosis. Mouse model of induced carotid atherosclerosis was established in the novel spontaneous HU Uox-KO mouse and their wild type littermates (C57BL/6J background). Mice were implanted with a perivascular collar placement around the right carotid artery in combination with a western-type diet. To investigate urate-lowering treatment (ULT) effects on intima, the mice were gavaged daily from the age of 6 weeks with allopurinol. Human umbilical vein endothelial cells (HUVECs) were co-incubated with soluble urate, with and without probenecid, to study the mechanism of urate-related atherosclerosis. The Uox-KO mice had significantly elevated serum urate levels combined with higher blood urea nitrogen and serum creatinine. Western blot analysis showed enhanced levels of atherosclerosis inflammatory response proteins. However, there were no other risk indicators for the pathogenesis of atherosclerosis, including increased fasting glucose, altered lipid and atherosclerosis characterized cardiovascular and histological manifestations. In contrast, collar placement Uox-KO mice showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA) - and F4/80-positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice accompanied by decreased expression of PCNA- and F4/80-positive cells (P< 0.05). ULT alleviated atherosclerosis inflammatory response factors and reactive oxygen species intensities in both collar placement Uox-KO mice and urate-stimulated HUVECs. In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate-lowering therapy partially abrogates the effects. The current study warrants the further human based study on the possible benefits of urate-lowering therapy in atherosclerosis patients with HU.

Summary statement

We generated a carotid collar placement atherosclerosis model in the novel spontaneous HU Uox-KO mouse and demonstrate that urate plays a contributing rather than a causal role in the carotid neointimal lesions, while urate-lowering treatment may bring additional benefits in this HU mouse model.
Silencing of ANKRD12 circRNA induces molecular and functional changes associated with invasive phenotypes
Authors: Karedath Thasni , Ahmed Ikhlak , Ameri Wafa Al , Al-Dasim Fatima M. , Andrews Simeon S. , Samuel Samson , Al-Azwani Iman K. , Mohamoud Yasmin Ali , Rafii Arash , Malek Joel A.
Published: July 2018

Circular RNAs (circRNA) that form through non-canonical backsplicing events of pre-mRNA transcripts are evolutionarily conserved and abundantly expressed across species. However, the functional relevance of circRNAs remains a topic of debate. In this study, we identified and characterized a circular RNA derived from Exon 2 and Exon 8 of the ANKRD12 gene, termed here as circANKRD12. We show that this circRNA is abundantly expressed in breast and ovarian cancers. The circANKRD12 is RNase R resistant and predominantly localized in the cytoplasm in contrast to its source gene mRNA. We confirmed the expression of this circRNA across a variety of cancer cell lines and provide evidence for its functional relevance through downstream regulation of several tumor invasion genes. We show that silencing of circANKRD12 induces a phenotypic change by significantly regulating cell cycle, increasing invasion and migration, altering the metabolism in cancer cells. These results reveal the functional significance of circANKRD12 and provide evidence of a regulatory role for this circRNA in cancer progression.
Structural differences between pri-miRNA paralogs promotes alternative Drosha cleavage and expands target repertoires
Authors: Ros Xavier Bofill-De , Kasprzak Wojciech K. , Bhandari Yuba , Fan Lixin , Cavanaugh Quinn , Jiang Minjie , Dai Lisheng , Yang Acong , Shao Tie-Juan , Shapiro Bruce A. , Wang Yun-Xing , Gu Shuo
Published: July 2018

MicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream processing and mature miRNA target specificity. To understand how pri-miRNA sequence and structure influence Drosha cleavage, we studied the maturation of three pri-miR-9 paralogs, which encode the same mature miRNA but differ in the surrounding scaffold. We show that pri-miR-9-1 has a unique Drosha cleavage profile due to its distorted and flexible stem structure. Cleavage of pri-miR-9-1, but not pri-miR-9-2 or pri-miR-9-3, generates an alternative-miR-9 with a shifted seed sequence that expands the scope of its target RNAs. Analyses of low grade glioma patient samples indicate that the alternative-miR-9 plays a distinct role in preventing tumor progression. To generalize our model, we provide evidence that distortion of pri-miRNA stems correlates with Drosha cleavage at non-canonical sites. Our studies reveal that pri-miRNA paralogs can have distinct functions via differential Drosha processing.
Translational initiation factor eIF5 replaces eIF1 on the 40S ribosomal subunit to promote start-codon recognition
Authors: Llácer Jose L. , Hussain Tanweer , Saini Adesh K. , Nanda Jagpreet , Kaur Sukhvir , Gordiyenko Yuliya , Kumar Rakesh , Hinnebusch Alan G. , Lorsch Jon R. , Ramakrishnan V.
Published: July 2018

In eukaryotic translation initiation AUG recognition of the mRNA requires accommodation of Met-tRNAiin a “PIN” state, which is antagonized by the factor eIF1. eIF5 is a GTPase activating protein (GAP) of eIF2 that additionally promotes stringent AUG selection, but the molecular basis of its dual function was unknown. We present a cryo-electron microscopy (cryo-EM) reconstruction of a 48S pre-initiation complex (PIC), at an overall resolution of 3.0 Å, featuring the N-terminal domain (NTD) of eIF5 bound to the 40S subunit at the location vacated by eIF1. eIF5 interacts with and allows a more accommodated orientation of Met-tRNAi. Substitutions of eIF5 residues involved in the eIF5-NTD/tRNAiinteraction influenced initiation at near-cognate UUG codonsin vivo, and the closed/open PIC conformationin vitro, consistent with direct stabilization of the codon:anticodon duplex by the wild-type eIF5-NTD. The present structure reveals the basis for a key role of eIF5 in start-codon selection.
Demultiplexing barcoded Oxford Nanopore reads with deep convolutional neural networks
Authors: Wick Ryan R. , Judd Louise M. , Holt Kathryn E.
Published: July 2018

Multiplexing, the simultaneous sequencing of multiple barcoded DNA samples on a single flow cell, has made Oxford Nanopore sequencing cost-effective for small genomes. However, it depends on the ability to sort the resulting sequencing reads by barcode, and current demultiplexing tools fail to classify many reads. Here we present Deepbinner, a tool for Oxford Nanopore demultiplexing that uses a deep neural network to classify reads based on the raw electrical read signal. This ‘signal-space’ approach allows for greater accuracy than existing ‘base-space’ tools (Albacore and Porechop) for which signals must first be converted to DNA base calls, itself a complex problem that can introduce noise into the barcode sequence. To assess Deepbinner and existing tools, we performed multiplex sequencing on 12 amplicons chosen for their distinguishability. This allowed us to establish a ground truth classification for each read based on internal sequence alone. Deepbinner had the lowest rate of unclassified reads (7.8%) and the highest demultiplexing precision (98.5% of classified reads were correctly assigned). It can be used alone (to maximise the number of classified reads) or in conjunction with other demultiplexers (to maximise precision and minimise false positive classifications). We also found cross-sample chimeric reads (0.3%) and evidence of barcode switching (0.3%) in our dataset, which likely arise during library preparation and may be detrimental for quantitative studies that use multiplexing. Deepbinner is open source (GPLv3) and available at https://github.com/rrwick/Deepbinner.
Orienting to Polarized Light at Night—Matching Lunar Skylight to Performance in a Nocturnal Beetle
Authors: Foster James J. , Kirwan John D. , Jundi Basil el , Smolka Jochen , Khaldy Lana , Baird Emily , Byrne Marcus J. , Nilsson Dan-Eric , Johnsen Sönke , Dacke Marie
Published: July 2018

For polarized light to inform behaviour, the typical range of degrees of polarization observable in the animal’s natural environment must be above the threshold for detection and interpretation. Here we present the first investigation of the degree of linear polarization threshold for orientation behaviour in a nocturnal species, with specific reference to the range of degrees of polarization measured in the night sky. An effect of lunar phase on the degree of polarization of skylight was found, with smaller illuminated fractions of the moon’s surface corresponding to lower degrees of polarization in the night sky. We found that South African dung beetleEscarabaeus satyrus(Boheman, 1860) can orient to polarized light for a range of degrees of polarization similar to that observed in diurnal insects, reaching a lower threshold between 0.04 and 0.32, possibly as low as 0.11. For degrees of polarization lower than 0.23, as measured on a crescent moon night, orientation performance was considerably weaker than that observed for completely linearly-polarized stimuli, but was nonetheless stronger than in the absence of polarized light.

Summary Statement

A degree-of-polarization threshold for orientation behaviour is reported for nocturnal dung beetleEscarabaeus satyrusin the context of measurements showing changes in the degree of polarization of skylight with lunar phase.
Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila
Authors: Di Cara Francesca , Rachubinski Richard A. , Simmonds Andrew J.
Published: July 2018

Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (Peroxin, PEX) cause progressive developmental disabilities and, in severe cases, early death. PEX5 and PEX7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix. We characterized mutants of Drosophila melanogaster Pex5 and Pex7 and found that adult animals are affected in lipid processing. Moreover, Pex5 mutants exhibited severe developmental defects in the embryonic nervous system and muscle, similar to what is observed in humans with Pex5 mutations, while Pex7 fly mutants were weakly affected in brain development, suggesting different roles for Pex7 in fly and human. Of note, although no PTS2-containing protein has been identified in Drosophila, Pex7 from Drosophila can function as a bona fide PTS2 receptor because it can rescue targeting of the PTS2-containing protein Thiolase to peroxisomes in PEX7 mutant human fibroblasts.
sigLASSO: optimizing cancer mutation signatures jointly with sampling likelihood
Authors: Li Shantao , Crawford Forrest W. , Gerstein Mark B.
Published: July 2018

Multiple mutational processes drive carcinogenesis, leaving characteristic signatures on tumor genomes. Determining the active signatures from the full repertoire of potential ones can help elucidate mechanisms underlying cancer initiation and development. This task in-volves decomposing the counts of cancer mutations, tabulated according to their trinucleotide context, into a linear combination of known mutational signatures. We formulate it as an optimization problem and develop sigLASSO, a software tool, to carry it out efficiently. (An R package implementation is available atgithub.com/gersteinlab/siglasso). sigLASSO features four key aspects: (1) It jointly optimizes the likelihood of sampling and signature fitting, by explicitly adding multinomial sampling into the overall objective function. This is particularly important when mutation counts are low and sampling variance is high, such as in exome sequencing. (2) sigLASSO uses L1 regularization to parsimoniously assign signatures to mutation profiles, leading to sparse and more biologically interpretable solutions resembling previously well-characterized results. (3) sigLASSO fine-tunes model complexity, informed by the scale of the data and biological-knowledge based priors. In particular, instead of hard thresholding and choosing a priori a discrete subset of active signatures, sigLASSO allows continuous priors, which can be effectively learned from auxiliary information. (4) Because of this, sigLASSO can assess model uncertainty and abstain from making certain assignments in low-confidence contexts. Finally, to evaluate sigLASSO signature assignments in comparison to other approaches, we develop a set of reasonable expectations (e.g. sparsity, the ability to abstain, and robustness to noise) that we apply consistently in a variety of contexts.
The expanded universe of prokaryotic Argonaute proteins
Authors: Ryazansky Sergei , Kulbachinskiy Andrey , Aravin Alexei A.
Published: July 2018

The members of the ancient family of Argonaute (Ago) proteins are present in all domains of life. The common feature of Ago proteins is the ability to bind small nucleic acid guides and use them for sequence-specific recognition – and sometimes cleavage – of complementary targets. While eukaryotic Ago (eAgo) proteins are key players in RNA interference and related pathways, the properties and functions of these proteins in archaeal and bacterial species have just started to emerge. We undertook comprehensive exploration of prokaryotic Ago (pAgo) proteins in sequenced genomes and almost tripled the number of previously analyzed genes of this family. In comparison with eAgos, pAgos are highly diverse and have likely spread by horizontal gene transfer. Many pAgos contain divergent variants of the conserved domains involved in interactions with nucleic acids and in target cleavage, while having extra domains that are absent in eAgos, suggesting that they might have unusual specificities in the nucleic acid recognition and processing. Many pAgos, including catalytically inactive variants, are associated with putative nucleases, helicases and DNA binding proteins in the same gene or operon, suggesting that they are involved in DNA processing. The great diversity of pAgos revealed by our analysis opens new ways for exploration of their functions in host cells and their use as potential tools in genome editing.
The role of the chief process officer in organizations
Authors: Kratzer Simon , Lohmann Patrick , Roeglinger Maximilian , Rupprecht Lea , zur Muehlen Michael
Published: July 2018

Purpose

The design and execution of business processes are important drivers of organizational performance. Organizations design their operations around cross-functional processes adopting business process management (BPM) methods, tools and systems. This often involves assigning BPM accountability to senior executives such as the chief operating officer (COO), chief information officer (CIO), or chief technology officer (CTO). Some organizations appoint a chief process officer (CPO), a phenomenon raising important questions about the skills and responsibilities of this position within the top management team. The purpose of this paper is to conduct an empirical study to explore the skills and responsibilities of CPOs and differences to other executives.

Design/methodology/approach

The authors conducted an exploratory content analysis of job resumes from LinkedIn.com to investigate the skills and careers of individuals appointed as COO, CIO, CTO and CPO in organizations from different industries and sizes. The content analysis was complemented with expert interviews of CPOs to obtain rich insights into their perception of the responsibilities of this position.

Findings

CPOs possess a unique skill set to serve as change agents. Their skills enable them to serve as integrators and influencers across managerial ranks and corporate functions. COOs, CIOs and CTOs possess more specialized skills related to their corporate function, whereas CPOs are more generalists who facilitate process-oriented strategy and execution, driving cultural change throughout the organization. These findings are consistent across industry and size.

Originality/value

This is the first paper to examine the CPO position in relation to other senior executive positions. Hence, it addresses an important gap in the BPM literature which can help organizations to make informed decisions whether they need a CPO position or have it become a part-time role of one of their existing C-level positions.
Housing wealth effects for private and subsidized homeowners
Authors: Wong Siu Kei , Deng Kuang Kuang , Cheung Ka Shing
Published: July 2018

Purpose

This paper aims to examine the effect of housing wealth on household consumption when there are resale and refinancing constraints that prevent housing assets from being cashed out.

Design/methodology/approach

Based on Household Expenditure Survey data in Hong Kong from 1999 to 2010, regression analysis is applied to compare the housing wealth effects of private and subsidized homeowners. Propensity score matching is adopted to ensure that the two groups of homeowners share similar household income. Further regression analysis is conducted to examine private homeowners’ consumption when their recourse mortgages are in negative equity.

Findings

Subsidized homeowners, who are not allowed to resell their units before sharing their capital gain with the government, experienced an insignificant housing wealth effect. While private homeowners experienced a significant housing wealth effect, the effect was weakened in the presence of a resale constraint induced by negative equity. The results remain robust after the application of more rigorous sample selection through propensity score matching.

Research limitations/implications

The analyses are subject to two potential data limitations. One is a relatively small sample size. The other is that data on financial assets and mortgages are unavailable and have to be indirectly controlled through household characteristics. Nevertheless, our estimated marginal propensity to consume out of housing wealth is 0.03 of the annual household consumption for private homeowners, which is within the range of estimates reported in previous literature.

Practical implications

This study shows that the housing wealth effect enjoyed in the private sector does not necessarily apply to the subsidized sector where resale and refinancing constraints exist. This is not to suggest that the constraints be removed. Rather, policymakers should be aware of the tradeoff: while the constraints ensure that government subsidies are used to assist home ownership, not capital gain, they also bring about consumption inequality in a society, especially in a booming housing market.

Originality/value

Our findings extend the literature on the housing wealth effect, which has been exclusively focusing on private homeowners, to subsidized homeowners. This study also adds to the literature on housing welfare by highlighting that the resale constraints of subsidized housing can weaken the housing wealth effect.
Cross-trained worker assignment and comparative analysis on throughput of divisional and rotating seru
Authors: Wu Lang , Chan Felix T.S. , Niu Ben , Li Li
Published: July 2018

Purpose

Seru (cell) manufacturing system has achieved huge success in production. However, related research is limited, especially, the problem of cross-trained worker assignment. The purpose of this paper is to solve this problem for two representative seru types, divisional and rotating seru, and subsequently, compare throughput performance between the two seru types under reasonable worker-task assignment.

Design/methodology/approach

For the cross-trained worker assignment problem, this research presents new models aiming at maximum throughput of seru and workload balance of workers under considering skill levels (SLs) and several practical constraints. Furthermore, factorial experiments that involve four factors, the number of tasks (NT), gap of task time, SL and gap of SL, are performed to compare throughput performance between divisional and rotating seru.

Findings

First, the maximum throughput of the divisional seru is better than that of the rotating seru under suitable worker assignment. Second, in the seru which has less difference of task time, throughput performance of the rotating seru is better than the divisional seru when the NT is close to the number of assigned workers. Moreover, the influence tendency of the four factors on throughput gap between the two seru types is significant.

Originality/value

This research addresses the worker-task assignment for divisional and rotating seru based on their characteristics. Several findings can help decision maker select more applicable seru type according to various production environments from the perspective of optimum throughput.
Entrepreneurial ecosystems: a systematic review
Authors: Maroufkhani Parisa , Wagner Ralf , Wan Ismail Wan Khairuzzaman
Published: July 2018

Purpose

The literature on entrepreneurial ecosystems is fragmented, and yet, no studies have paid attention to integrating the available studies. The purpose of this study is to provide a systematic review of contributions related to entrepreneurial ecosystems.

Design/methodology/approach

This literature review evaluates studies that are covered in the Web of Science index.

Findings

In addition to the recent state of research (covering industries, geographical scopes, methodologies, etc.), this study provides an extension of Isenberg’s (2011) model of entrepreneurial ecosystems.

Research limitations/implications

A new avenue arises for both conceptual and empirical research by emphasizing crowdsourcing as a contributing element for the entrepreneurial ecosystem. Future studies can evaluate the effectiveness of different types of crowdsourcing profoundly to make sure whether creating a promising ecosystem all types of crowdsourcing have a similar value or impact.

Practical implications

For public policy and local decision-makers, both collaboration opportunities and interaction interfaces between the stakeholders of the entrepreneurial need to be reconsidered in the design of entrepreneurial ecosystems.

Social implications

Higher degrees of collaboration, information exchange and innovation are likely to yield favorable entrepreneurship environments.

Originality/value

Novelty of this study arises from integrating crowdsourcing theory in the systematic review of entrepreneurial ecosystems.
Service user perspectives of an early intervention in psychosis service: a service evaluation
Authors: Watkins Simon , Sanderson Chris , Richards Victoria
Published: July 2018

Purpose

The purpose of this paper is to gather the perspectives of individuals accessing an early intervention in psychosis service (EIPS), in order to inform service development.

Design/methodology/approach

Individual interviews (n=9) and one focus group (n=7) were conducted. Discussions focused on open questions pertaining to service users’ (SU’s) experiences of accessing the EIPS. The results were analysed using inductive thematic analysis.

Findings

Inductive thematic analysis was used and three main themes were generated: consistency and communication, facilitating therapeutic relationships between EIPS staff and SU’s; pushing boundaries, relating to the importance of services taking a graded approach to developing therapeutic relationships and (re)engaging in activities; and normalising and validating experiences of psychosis. Participants emphasised the importance of relationships with EIPS staff and fellow SUs and highlighted how SUs can feel fearful and vulnerable when staff are not accessible or they view their care as inconsistent. Participants further emphasised the need for practitioners to balance an approach that de-stigmatises psychotic experiences whilst validating distress.

Practical implications

Consistency of support from EIPSs can be as important as flexibility. Clinicians should carefully consider the balance between validating and normalising distressing experiences associated with psychosis. Offering social activities with other SUs can facilitate therapeutic relationships and recovery but the results suggest that this should be facilitated in a graded way.

Originality/value

The paper addresses current need in the literature to understand the experiences of people using services in order to improve the quality of the services provided.
Empowering subsistence women entrepreneurs in India
Authors: Saripalli Bhavani Shankar , Chawan Vinaysingh , Gunta Srinivas
Published: July 2018

Purpose

Empowerment of women by social enterprises in emerging economies has received attention from researchers. This paper aims to study three social enterprises in India that aim to empower subsistence women entrepreneurs.

Design/methodology/approach

A comparative case analysis of three social enterprises is done to develop understanding of systems and processes adopted by them. Sources such as published journal and news articles, case studies, success stories and official websites are used for data collection.

Findings

The study found that all three organisations strive to increase the asset base of members by organizing disempowered subsistence producers lacking market power; extending services throughout the value chain, i.e. from raw material supply to marketing of products; ploughing back regular incomes and bonuses through mechanisms acceptable to all members; and empowering subsistence producers to gain market power and ability to choose. The interventions give market exposure and voice to the concerns of women producers. These organisations successfully leverage the strength of their relations with civil society and markets in sustaining the business. Women empowerment was found to be achieved through regular income, collective voice, ability to take decisions and creation of social value.

Research limitations/implications

This paper does not take into consideration enterprises promoted by government.

Practical implications

A conceptual framework is suggested in this paper along with insights for organisations interested in collectivising subsistence women for empowering them.

Originality/value

The conceptual framework provided in this paper enriches the understanding of social enterprises working with the objective of women empowerment.
Association of characteristics of people with type 2 diabetes mellitus with discordant values of fasting glucose and HbA1c
Authors: Rathmann Wolfgang , Bongaerts Brenda , Kostev Karel
Published: July 2018

Background

Primary care physicians frequently encounter people with type 2 diabetes mellitus (T2DM) with discordant values for fasting glucose and HbA1c. The aim of this study was to identify the prevalence and characteristics of people in whom blood glucose and HbA1c did not match.

Methods

Overall, 64 553 people with T2DM from 939 general or internal medicine practices (Disease Analyzer database, Germany; January 2013–December 2015) were analyzed. Multivariable logistic regression models were used to identify associations between baseline clinical characteristics, comorbidity, and glucose‐lowering treatment and discordance of fasting glucose and HbA1c values measured at the same visit.

Results

Overall, 8582 (13%) patients had fasting glucose ≥140 mg/dL and HbA1c <7% (<53 mmol/mol), and 6508 (10%) had HbA1c ≥7% (≥53 mmol/mol) and fasting glucose <140 mg/dL. Using patients with both fasting glucose <140 mg/dL and HbA1c <7% as the reference (n = 31 834; 49%), solitary high fasting glucose values (and HbA1c <7%) were positively associated with higher age, male sex, longer diabetes duration, obesity, liver disease, low estimated glomerular filtration rate (eGFR), and glucose‐lowering treatment. High HbA1c (and fasting glucose <140 mg/dL) was positively related to longer diabetes duration, obesity, neuropathy, retinopathy, low eGFR, and insulin treatment. There were lower odds of having solitary increased HbA1c ≥7% (fasting glucose <140 mg/dL) with higher age, hypertension, depression, and the number of diabetes patients (>200) per practice.

Conclusions

A considerable number of people with T2DM in primary care practices have discordant fasting blood glucose and HbA1c values. People who have discordant glycemic values have different characteristics.
ConcaveCubes: Supporting Cluster‐based Geographical Visualization in Large Data Scale
Authors: Li Mingzhao , Choudhury Farhana , Bao Zhifeng , Samet Hanan , Sellis Timos
Published: July 2018

In this paper we study the problem of supporting effective and scalable visualization for the rapidly increasing volumes of urban data. From an extensive literature study, we find that the existing solutions suffer from at least one of the drawbacks below: (i) loss of interesting structures/outliers due to sampling; (ii) supporting heatmaps only, which provides limited information; and (iii) no notion of real‐world geography semantics (e.g., country, state, city) is captured in the visualization result as well as the underlying index. Therefore, we propose ConcaveCubes, a cluster‐based data cube to support interactive visualization of large‐scale multidimensional urban data. Specifically, we devise an appropriate visualization abstraction and visualization design based on clusters. We propose a novel concave hull construction method to support boundary based cluster map visualization, where real‐world geographical semantics are preserved without any information loss. Instead of calculating the clusters on demand, ConcaveCubes (re)utilizes existing calculation and visualization results to efficiently support different kinds of user interactions. We conduct extensive experiments using real‐world datasets and show the efficiency and effectiveness of ConcaveCubes by comparing with the state‐of‐the‐art cube‐based solutions.
Landscaper: A Modeling System for 3D Printing Scale Models of Landscapes
Authors: Allahverdi K. , Djavaherpour H. , Mahdavi‐Amiri A. , Samavati F.
Published: July 2018

Landscape models of geospatial regions provide an intuitive mechanism for exploring complex geospatial information. However, the methods currently used to create these scale models require a large amount of resources, which restricts the availability of these models to a limited number of popular public places, such as museums and airports. In this paper, we have proposed a system for creating these physical models using an affordable 3D printer in order to make the creation of these models more widely accessible. Our system retrieves GIS relevant to creating a physical model of a geospatial region and then addresses the two major limitations of affordable 3D printers, namely the limited number of materials and available printing volume. This is accomplished by separating features into distinct extruded layers and splitting large models into smaller pieces, allowing us to employ different methods for the visualization of different geospatial features, like vegetation and residential areas, in a 3D printing context. We confirm the functionality of our system by printing two large physical models of relatively complex landscape regions.