bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable Prediction of mRNA Abundance from Promoter Sequence using Contextual Regression Models
Authors: Wang Song , Wang Wei 
Published: August 2022

AbstractWhile machine learning models have been successfully applied to predicting gene expression from promoter sequences, it remains a great challenge to derive intuitive interpretation of the model and reveal DNA motif grammar such as motif cooperation and distance constraint between motif sites. Previous interpretation approaches are often time-consuming or hard to learn the combinatory rules. In this work, we designed interpretable neural network models to predict the mRNA expression levels from DNA sequences. By applying the Contextual Regression framework we developed, we extracted weighted features to cluster samples into different groups, which have different gene expression levels. We performed motif analysis in each cluster and found motifs with active or repressive regulation on gene expression as well as motif combination grammars including several motif communities and distance constraints between cooperative motifs.
IndepthPathway: an integrated tool for in-depth pathway enrichment analysis based on bulk and single cell sequencing data
Authors: Lee Sanghoon , Deng Letian , Wang Yue , Wang Kai , Sartor Maureen A. , Wang Xiaosong 
Published: August 2022

ABSTRACTSingle-cell sequencing (SCS) enables exploring the pathways and processes of cells, and cell populations. However, there is a paucity of pathway enrichment methods designed to tolerate the high noise and low gene coverage of this technology. When gene expression data are noisy and signals are sparse, testing pathway enrichment based on the genes expression may not yield statistically significant results which is particularly problematic when detecting the pathways enriched in less abundant cells that are vulnerable to disturbances. In this project, we developed a Weighted Concept Signature Enrichment Analysis (WCSEA) algorithm specialized for pathway enrichment analysis from single cell transcriptomics (scRNA-seq). WCSEA took a broader approach for assessing the functional relations of pathway gene sets to differentially expressed genes, and leverage the cumulative signature of molecular concepts characteristic of the highly differentially expressed genes, which we termed as the universal concept signature, to tolerate the high noise and low coverage of this technology. We then incorporated WCSEA into a R package called “IndepthPathway” for biologists to broadly leverage this method for pathway analysis based on bulk and single cell sequencing data. Through simulating technical variability and dropouts in gene expression characteristic of scRNA-seq as well as benchmarking on a real dataset of matched single cell and bulk RNAseq data, we demonstrate that IndepthPathway presents outstanding stability and depth in pathway enrichment results under stochasticity of the data, thus will substantially improve the scientific rigor of the pathway analysis for single cell sequencing data. The IndepthPathway package is available through:https://github.com/wangxlab/IndepthPathway.
Predicting anti-cancer drug synergy using extended drug similarity profiles
Authors: Hosseini Sayed-Rzgar , Zhou Xiaobo 
Published: August 2022

AbstractCombination therapy is a promising strategy for confronting the complexity of cancer. However, experimental exploration of the vast space of potential drug combinations is costly and unfeasible. Therefore, computational methods for predicting drug synergy are much-needed for narrowing down this space, especially when examining new cellular contexts. Here, we thus introduce CCSynergy, a flexible, context-aware and integrative deep learning framework that we have established to unleash the potential of the Chemical Checker extended drug similarity profiles for the purpose of drug synergy prediction. We have shown that CCSynergy enables predictions of superior accuracy, remarkable robustness and improved context-generalizability as compared to the state-of-the-art methods in the field. Having established the potential of CCSynergy for generating experimentally validated predictions, we exhaustively explored the untested drug combination space. This resulted in a compendium of potentially synergistic drug combinations on hundreds of cancer cell lines, which can guide future experimental screens.
FAVOR: Functional Annotation of Variants Online Resource and Annotator for Variation across the Human Genome
Authors: Zhou Hufeng , Arapoglou Theodore , Li Xihao , Li Zilin , Zheng Xiuwen , Moore Jill , Asok Abhijith , Kumar Sushant , Blue Elizabeth E. , Buyske Steven , Cox Nancy , Felsenfeld Adam , Gerstein Mark , Kenny Eimear , Li Bingshan , Matise Tara , Philippakis Anthony , Rehm Heidi , Sofia Heidi J. , Snyder Grace ,   NHGRI Genome Sequencing Program Variant Functional Annotation Working Group, Weng Zhiping , Neale Benjamin , Sunyaev Shamil R. , Lin Xihong 
Published: August 2022

ABSTRACTLarge-scale whole genome sequencing (WGS) studies and biobanks are rapidly generating a multitude of coding and non-coding variants. They provide an unprecedented resource for illuminating the genetic basis of human diseases. Variant functional annotations play a critical role in WGS analysis, result interpretation, and prioritization of disease- or trait-associated causal variants. Existing functional annotation databases have limited scope to perform online queries or are unable to functionally annotate the genotype data of large WGS studies and biobanks for downstream analysis. We develop the Functional Annotation of Variants Online Resources (FAVOR) to meet these pressing needs. FAVOR provides a comprehensive online multi-faceted portal with summarization and visualization of all possible 9 billion single nucleotide variants (SNVs) across the genome, and allows for rapid variant-, gene-, and region-level online queries. It integrates variant functional information from multiple sources to describe the functional characteristics of variants and facilitates prioritizing plausible causal variants influencing human phenotypes. Furthermore, a scalable annotation tool, FAVORannotator, is provided for functionally annotating and efficiently storing the genotype and variant functional annotation data of a large-scale sequencing study in an annotated GDS file format to facilitate downstream analysis. FAVOR and FAVORannotator are available at https://favor.genohub.org.
A CRISPR-Cas9-mediated F0 screen to identify pro-regenerative genes in the zebrafish retinal pigment epithelium
Authors: Lu Fangfang , Leach Lyndsay L. , Gross Jeffrey M. 
Published: August 2022

ABSTRACTOcular diseases resulting in death of the retinal pigment epithelium (RPE) lead to vision loss and blindness. There are currently no FDA-approved strategies to restore damaged RPE cells. Stimulating intrinsic regenerative responses within damaged tissues has gained traction as a possible mechanism for tissue repair. Zebrafish possess remarkable regenerative abilities, including within the RPE; however, our understanding of the underlying mechanisms remains limited. Here, we conducted an F0 in vivo CRISPR-Cas9-mediated screen of 27 candidate RPE regeneration genes. The screen involved injection of a ribonucleoprotein complex containing three highly mutagenic guide RNAs per target gene followed by PCR-based genotyping to identify large intragenic deletions and MATLAB-based automated quantification of RPE regeneration. Through this F0 screening pipeline, eight positive and seven negative regulators of RPE regeneration were identified. Further characterization of one candidate, cldn7b, revealed novel roles in regulating macrophage/microglia infiltration after RPE injury and in clearing RPE/pigment debris during late-phase RPE regeneration. Taken together, these data support the utility of targeted F0 screens for validating pro-regenerative factors and reveal novel factors that could regulate regenerative responses within the zebrafish RPE.Summary statementWe present a rapid CRISPR-Cas9-mediated F0 screen, which revealed novel regulators of retinal pigment epithelium (RPE) regeneration in zebrafish. This screen and identified factors will greatly facilitate discovery of underlying RPE regenerative mechanisms.
Plumage colouration differs between offspring raised in natural cavities and nestboxes
Authors: Janas Katarzyna , Lecce Irene Di , Szulkin Marta , Sudyka Joanna 
Published: August 2022

AbstractMost of our knowledge on hole-nesting birds, including plumage colouration (an important component of visual signalling), comes from studies on populations breeding in human-provided nestboxes. However, as demonstrated in comparative studies, multiple parameters, such as cavity dimensions and microclimatic conditions, differ between natural and artificial cavities. Despite this, no study so far examined the impact of cavity type on plumage colouration to verify whether extrapolation of results from birds growing in nestboxes is justified. Here, we examined the impact of cavity type – natural cavities vs. nestboxes - on the carotenoid-based colouration of blue tit (Cyanistes caeruleus) and great tit (Parus major) nestlings. We found clear differences in plumage colouration depending on the type of cavity in which the birds developed. Our study adds to the growing body of evidence confirming that varying properties of natural cavities and nestboxes might influence nestling physiology, leading to phenotypic differences in the long-term.
Controlling for false discoveries subsequently to large scale one-way ANOVA testing in proteomics: practical considerations
Authors: Burger Thomas 
Published: August 2022

AbstractIn discovery proteomics, as well as many other “omic” approaches, the possibility to test for the differential abundance of hundreds (or of thousands) of features simultaneously is appealing, despite requiring specific statistical safeguards, among which controlling for the False Discovery Rate (FDR) has become standard. Moreover, when more than two biological conditions or group treatments are considered, it has become customary to rely on the one-way Analysis of Variance (ANOVA) framework, where a first global differential abundance landscape provided by an omnibus test can be subsequently refined using various post-hoc tests. However, the interactions between the FDR control procedures and the post-hoc tests are complex, because both correspond to different types of multiple test corrections. This article surveys various ways to orchestrate them in a data processing workflow and discusses their pros and cons.
The Immunological Proteome Resource
Authors: Brenes Alejandro J. , Hukelmann Jens L. , Spinelli Laura , Howden Andrew J.M. , Marchingo Julia M. , Sinclair Linda V. , Rollings Christina , James Olivia J. , Phair Iain R , Matthews Stephen P. , Ross Sarah H. , Arthur J. Simon C. , Swamy Mahima , Finlay David K. , Lamond Angus I. , Cantrell Doreen A. 
Published: August 2022

AbstractThe Immunological Proteome Resource (ImmPRes;http://immpres.co.uk/) is an open access public resource integrating proteomic data generated by large-scale mass-spectrometry analysis of murine hematopoietic populations. The initial focus is T lymphocytes and how their proteomes are shaped by immune activation, environment, and intracellular signalling pathways with an aim to expand it to B cells and innate immune cells. It is a multidisciplinary effort between immunology and mass spectrometry-based labs with the objective to help define an in-depth high-quality map of immune cell proteomes. Maintaining data reproducibility and integrity are a priority within the resource, thus there is an in-depth protocols section explaining in detail the sample processing and the mass spectrometry-based analysis. ImmPRes provides open access to proteomic datasets covering a wide range of murine leukocyte populations with analysis of copy numbers per cell of > 10,000 proteins, enabling new understanding of lymphocyte phenotypes. All data is accessible via a simple graphical interface that supports easy interrogation of the data and options to download data summaries and raw data files.
Locus Coeruleus firing patterns selectively modulate brain activity and dynamics
Authors: Grimm Christina , Duss Sian N. , Privitera Mattia , Munn Brandon R. , Frässle Stefan , Chernysheva Maria , Patriarchi Tommaso , Razansky Daniel , Wenderoth Nicole , Shine James M. , Bohacek Johannes , Zerbi Valerio 
Published: August 2022

AbstractNoradrenaline (NA) release from the brainstem nucleus locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, thus modulating multiple behavioural states. NA release is mediated by both tonic and burst-like neuronal LC activity. However, it remains unknown whether the functional changes in downstream projection areas depend on these firing patterns. Using optogenetics, pupillometry, photometry, and functional MRI in mice, we show that tonic and burst LC firing patterns elicit brain responses that are specific to the activation frequency and temporal pattern. Tonic activation of the LC evokes nonlinear responses in prefrontal, limbic, and cerebellar regions, in line with the proposed inverted-U relationship between LC activity and behaviour. We further demonstrate that LC activity enhances network integration and acts as a facilitator of brain state transitions, hence increasing brain flexibility. Together, these findings reveal how the LC-NA system achieves a nuanced regulation of global circuit operations.
AcaFinder: genome mining for anti-CRISPR associated genes
Authors: Yang Bowen , Zheng Jinfang , Yin Yanbin 
Published: August 2022

AbstractAnti-CRISPR (Acr) proteins are encoded by (pro)viruses to inhibit their host’s CRISPR-Cas systems. Genes encoding Acr and Aca (Acr associated) proteins often co-localize to form acr-aca operons. Here, we present AcaFinder as the first Aca genome mining tool. AcaFinder can: (i) predict Acas and their associated acr-aca operons using guilt-by-association (GBA); (ii) identify homologs of known Acas using an HMM (Hidden Markov model) database; (iii) take input genomes for potential prophages, CRISPR-Cas systems, and self-targeting spacers (STSs); and (iv) provide a standalone program (https://github.com/boweny920/AcaFinder) and a web server (http://aca.unl.edu/Aca). AcaFinder was applied to mining over 16,000 prokaryotic and 142,000 gut phage genomes. After a multi-step filtering, 36 high-confident new Aca families were identified, which is three times of the 12 known Aca families. Seven new Aca families were from major human gut bacteria (Bacteroidota, Actinobacteria, Fusobacteria) and their phages, while most known Aca families were from Proteobacteria and Firmicutes. A complex association network between Acrs and Acas was revealed by analyzing their operonic co-localizations. It appears very common in evolution that the same aca genes can recombine with different acr genes and vice versa to form diverse acr-aca operon combinations.ImportanceAt least four bioinformatics programs have been published for genome mining of Acrs since 2020. In contrast, no bioinformatics tools are available for automated Aca discovery. As the self-transcriptional repressor of acr-aca operons, Aca can be viewed as anti-anti-CRISPRs, with a great potential in the improvement of CRISPR-Cas technology. Although all the 12 known Aca proteins contain a conserved Helix-Turn-Helix (HTH) domain, not all HTH-containing proteins are Acas. However, HTH-containing proteins with an adjacent Acr homologs encoded in the same genetic operon are likely Aca proteins. AcaFinder implements this guilt-by-association (GBA) idea and the idea of using HMMs of known Acas for homologs into one software package. Applying AcaFinder in screening prokaryotic and gut phage genomes reveals a complex acr-aca operonic co-localization network between different families of Acrs and Acas.
How does contract flexibility affect the sustainability performance of public–private partnership projects? A serial multiple mediator model
Authors: Tian Bo , Fu Jiaxin , Xu Yongshun , Sun Longshan 
Published: August 2022

PurposeThe risks and uncertainties of public–private partnership (PPP) projects threaten their sustainability. Contract flexibility, which is based on the theory of incomplete contract and transaction cost, may be a viable solution to this issue. The purpose of this study is to investigate the relationship between contract flexibility and the sustainability performance of PPP projects. The multiple mediating roles of justice perception and cooperation efficiency are assessed, thereby allowing the pathways and conditions to be understood more comprehensively for improving the sustainability performance of PPP projects.Design/methodology/approachNine hypotheses in the proposed research model are tested via structural equation modeling using data acquired from 218 Chinese PPP professionals.FindingsResults show that contract flexibility positively affects PPP project sustainability performance. Justice perception and cooperation efficiency play direct and sequential mediating roles in this effect.Originality/valueThis study validates that contract flexibility positively impacts the sustainability performance of PPP projects, where justice perception and cooperation efficiency serve direct and sequential mediating roles. The findings of this study contribute to an improved understanding of the effect of contract flexibility on the sustainability performance of PPP projects. Furthermore, they provide important theoretical and practical insights into contract management as well as beneficial information and valuable initiatives for improving the sustainability of PPP projects.
India Post: its 21st-century avatar
Authors: Subramanian R. Bala , Thakur Munish 
Published: August 2022

Learning outcomes
The case has the following learning objectives: to assess the importance of the business environment, its impact on the organization and how the organization responds to the changes in the business environment; to apply the resource-based view of the organization and resource dependence theory; and to apply and analyze the organization’s strategic initiatives within the framework of the political, economic, social and technological analysis model, Porter’s five forces of business analysis and to make recommendations based on the above analysis.

Case overview/synopsis
The paradigm shift in technology has an impact on business. With 155,015 Post Offices, India Post has the most widely distributed postal network in the world. This case captures the journey of India Post from inception to its current form. Over its life, the organization has evolved because of multiple changes. But the recent changes have threatened to disrupt the organization. These changes have been induced by three major forces: technology, the rise of competition, especially foreign players, and social changes in urban and rural India because of changing consumption patterns as incomes rise and online retail grows. The organization has reacted to this threat by leveraging its resources to offer new products according to customer tastes by entering more unique industries and product categories. They have started logistics services in association with Indian railways and started offering retail services such as bill collection and college application forms. Also, they have created a financial division, “Payment Bank.” Thus, they have evolved from being a single entity of postal-related services to various services. The case poses a dilemma if these product diversifications are thriving as the organization’s product portfolio has diversified, given its existing capabilities and ability to create newer capabilities, particularly the payment bank.

Complexity academic level
The case is ideally suited for the discussion of resource-based view of the firm in the subject strategic management and organizational theory. The case can be used to discuss resource dependence theory as well. It is equally well suited to discuss the impact of environment in business in the subject organization theory and the impact of technology on change in the subject organizational change. The case is meant for MBA. The case can be used for executive audience as well.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.
Crowdsourced product returns in C2B e-commerce: a post-pandemic no-contact consumer incentive-based model
Authors: Kumar Chitresh , Ganguly Anirban 
Published: August 2022

Purpose
This study aims to investigate the conditions for the financial feasibility of an incentive-based model for self-drop or crowdsourced drop of the product to be returned at designated drop boxes (thereby ensuring a contactless process).

Design/methodology/approach
Constraint-based non-linear mathematical modeling was done for cost differential with and without crowdsourcing. This was analyzed against returns on investment for the installed infrastructure. Scenarios were looked into from the linear, iso-elastic and logarithmic demand functions to identify the optimal incentive policy. The results were further evaluated using “willingness to return” for customer willingness for product returns via drop boxes.

Findings
Crowdsourcing is viable when product returns are no more than 15%–20% of the overall products, with a logistics cost differential of 15%–25%. These were only viable when the product return incentive was within the range of 15%–20% of the product cost, as well as the penalty was in the range of 25 to 40% for wrong returns.

Research limitations/implications
The findings are expected to aid the organizations in successfully designing product return policies while adhering to the post-COVID-19 norms, including contactless transactions and social distancing.

Originality/value
The study provides a look into the viability sensitivity of effective gains/profitability against the required level of service for returns, wrong returns, penalties and incentives for crowdsourcing in a developing country like India.
Structural performance of single-skin glass façade systems exposed to fire
Authors: Badr Mohamed , Youssef Maged A. , El-Fitiany Salah , Vedrtnam Ajitanshu 
Published: August 2022

PurposeUnderstanding the structural performance of external glass curtain walls (façades) during fire exposure is critical for the safety of the occupants as their failure can lead to fire spread throughout the entire building. This concern is magnified by the recent increase in fire incidents and wildfires. This paper presents the first simplified technique to model single-skin façades during fire exposure and then utilizes it to examine the structural behaviour of vertical, inclined and oversized façade panels.Design/methodology/approachThe proposed technique is based on conducting simplified heat transfer calculations and then utilizing a widely used structural analysis software program to analyze the façade. Validation for the proposed technique with reference to available experimental and numerical studies by others is presented. A parametric study is then conducted to assess the structural performance of different glass façade systems during exposure to fire.FindingsThe proposed technique was found to provide accurate predictions of the structural performance of glass façades during fire exposure. The structural performance of inclined façade systems during fire exposure was found to be superior to vertical and oversized façade systems.Originality/valueThis research paper is the first to provide a simplified technique that can be utilized to model single-skin facades under fire. The presented technique along with the conducted parametric study will improve the understanding of the fire behaviour of single-skin glass facades, which will lead to safer applications.