cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12851424
title: Covariate Adaptive False Discovery Rate Control With Applications to Omics-Wide Multiple Testing

description: Conventional multiple testing procedures often assume hypotheses for different features are exchangeable. However, in many scientific applications, additional covariate information regarding the patterns of signals and nulls are available. In this article, we introduce an FDR control procedure in large-scale inference problem that can incorporate covariate information. We develop a fast algorithm to implement the proposed procedure and prove its asymptotic validity even when the underlying likelihood ratio model is misspecified and the <i>p</i>-values are weakly dependent (e.g., strong mixing). Extensive simulations are conducted to study the finite sample performance of the proposed method and we demonstrate that the new approach improves over the state-of-the-art approaches by being flexible, robust, powerful, and computationally efficient. We finally apply the method to several omics datasets arising from genomics studies with the aim to identify omics features associated with some clinical and biological phenotypes. We show that the method is overall the most powerful among competing methods, especially when the signal is sparse. The proposed covariate adaptive multiple testing procedure is implemented in the R package CAMT. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.12851424.v2
title: Covariate Adaptive False Discovery Rate Control With Applications to Omics-Wide Multiple Testing

description: Conventional multiple testing procedures often assume hypotheses for different features are exchangeable. However, in many scientific applications, additional covariate information regarding the patterns of signals and nulls are available. In this article, we introduce an FDR control procedure in large-scale inference problem that can incorporate covariate information. We develop a fast algorithm to implement the proposed procedure and prove its asymptotic validity even when the underlying likelihood ratio model is misspecified and the <i>p</i>-values are weakly dependent (e.g., strong mixing). Extensive simulations are conducted to study the finite sample performance of the proposed method and we demonstrate that the new approach improves over the state-of-the-art approaches by being flexible, robust, powerful, and computationally efficient. We finally apply the method to several omics datasets arising from genomics studies with the aim to identify omics features associated with some clinical and biological phenotypes. We show that the method is overall the most powerful among competing methods, especially when the signal is sparse. The proposed covariate adaptive multiple testing procedure is implemented in the R package CAMT. Supplementary materials for this article are available online.
DOI: 10.6084/m9.figshare.7608545
title: Additional file 3: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S3. List of 423 differentially expressed proteins in O. sativa upon BPH infestation. (XLSX 35 kb)
DOI: 10.6084/m9.figshare.7608545.v1
title: Additional file 3: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S3. List of 423 differentially expressed proteins in O. sativa upon BPH infestation. (XLSX 35 kb)
DOI: 10.6084/m9.figshare.12851426
title: <i>Burkholderia pseudomallei</i> interferes with host lipid metabolism via <i>NR1D2</i>-mediated <i>PNPLA2/ATGL</i> suppression to block autophagy-dependent inhibition of infection

description: <b>Burkholderia pseudomallei</b>: which causes melioidosis with high mortality in humans, has become a global public health concern. Recently, infection-driven lipid droplet accumulation has been related to the progression of host-pathogen interactions, and its contribution to the pathogenesis of infectious disease has been investigated. Here, we demonstrated that <i>B. pseudomallei</i> infection actively induced a time-dependent increase in the number and size of lipid droplets in human lung epithelial cells and macrophages. We also found that lipid droplet accumulation following <i>B. pseudomallei</i> infection was associated with downregulation of <i>PNPLA2/ATGL</i> (patatin like phospholipase domain containing 2) and lipophagy inhibition. Functionally, lipid droplet accumulation, facilitated via <i>PNPLA2</i> downregulation, inhibited macroautophagic/autophagic flux and, thus, hindered autophagy-dependent inhibition of <i>B. pseudomallei</i> infection in lung epithelial cells. Mechanistically, we further revealed that nuclear receptor <i>NR1D2</i> might be involved in the suppression of <i>PNPLA2</i> after cell exposure to <i>B. pseudomallei</i>. Taken together, our findings unraveled an evolutionary strategy, by which <i>B. pseudomallei</i> interferes with the host lipid metabolism, to block autophagy-dependent suppression of infection. This study proposes potential targets for clinical therapy of melioidosis. <b>Abbreviations</b>: 3-MA: 3-methyladenine; ACTB: actin beta; ATG7: autophagy related 7; <i>B. pseudomallei: Burkholderia pseudomallei</i>; CFU: colony-forming unit; DG: diglyceride; FASN: fatty acid synthase; GFP: green fluorescent protein; LAMP1: lysosomal associated membrane protein 1; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LD: lipid droplet; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MG: monoglyceride; MOI: multiplicity of infection; mRFP: monomeric red fluorescent protein; NR1D2: nuclear receptor subfamily 1 group D member 2; p.i., post-infection; PLIN2/ADRP: perilipin 2; PNPLA2/ATGL: patatin like phospholipase domain containing 2; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; shRNA: short hairpin RNA; TEM: transmission electron microscopy; TG: triglyceride
DOI: 10.6084/m9.figshare.12851426.v1
title: <i>Burkholderia pseudomallei</i> interferes with host lipid metabolism via <i>NR1D2</i>-mediated <i>PNPLA2/ATGL</i> suppression to block autophagy-dependent inhibition of infection

description: <b>Burkholderia pseudomallei</b>: which causes melioidosis with high mortality in humans, has become a global public health concern. Recently, infection-driven lipid droplet accumulation has been related to the progression of host-pathogen interactions, and its contribution to the pathogenesis of infectious disease has been investigated. Here, we demonstrated that <i>B. pseudomallei</i> infection actively induced a time-dependent increase in the number and size of lipid droplets in human lung epithelial cells and macrophages. We also found that lipid droplet accumulation following <i>B. pseudomallei</i> infection was associated with downregulation of <i>PNPLA2/ATGL</i> (patatin like phospholipase domain containing 2) and lipophagy inhibition. Functionally, lipid droplet accumulation, facilitated via <i>PNPLA2</i> downregulation, inhibited macroautophagic/autophagic flux and, thus, hindered autophagy-dependent inhibition of <i>B. pseudomallei</i> infection in lung epithelial cells. Mechanistically, we further revealed that nuclear receptor <i>NR1D2</i> might be involved in the suppression of <i>PNPLA2</i> after cell exposure to <i>B. pseudomallei</i>. Taken together, our findings unraveled an evolutionary strategy, by which <i>B. pseudomallei</i> interferes with the host lipid metabolism, to block autophagy-dependent suppression of infection. This study proposes potential targets for clinical therapy of melioidosis. <b>Abbreviations</b>: 3-MA: 3-methyladenine; ACTB: actin beta; ATG7: autophagy related 7; <i>B. pseudomallei: Burkholderia pseudomallei</i>; CFU: colony-forming unit; DG: diglyceride; FASN: fatty acid synthase; GFP: green fluorescent protein; LAMP1: lysosomal associated membrane protein 1; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LD: lipid droplet; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MG: monoglyceride; MOI: multiplicity of infection; mRFP: monomeric red fluorescent protein; NR1D2: nuclear receptor subfamily 1 group D member 2; p.i., post-infection; PLIN2/ADRP: perilipin 2; PNPLA2/ATGL: patatin like phospholipase domain containing 2; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; shRNA: short hairpin RNA; TEM: transmission electron microscopy; TG: triglyceride
DOI: 10.6084/m9.figshare.12851429
title: BNIP3L/NIX degradation leads to mitophagy deficiency in ischemic brains

description: Mitophagy, the elimination of damaged mitochondria through autophagy, promotes neuronal survival in cerebral ischemia. Previous studies found deficient mitophagy in ischemic neurons, but the mechanisms are still largely unknown. We determined that BNIP3L/NIX, a mitophagy receptor, was degraded by proteasomes, which led to mitophagy deficiency in both ischemic neurons and brains. BNIP3L exists as a monomer and homodimer in mammalian cells, but the effects of homodimer and monomer on mitophagy are unclear. Site-specific mutations in the transmembrane domain of BNIP3L (S195A and G203A) only formed the BNIP3L monomer and failed to induce mitophagy. Moreover, overexpression of wild-type BNIP3L, in contrast to the monomeric BNIP3L, rescued the mitophagy deficiency and protected against cerebral ischemic injury. The macroautophagy/autophagy inhibitor 3-MA and the proteasome inhibitor MG132 were used in cerebral ischemic brains to identify how BNIP3L was reduced. We found that MG132 blocked the loss of BNIP3L and subsequently promoted mitophagy in ischemic brains. In addition, the dimeric form of BNIP3L was more prone to be degraded than its monomeric form. Carfilzomib, a drug for multiple myeloma therapy that inhibits proteasomes, reversed the BNIP3L degradation and restored mitophagy in ischemic brains. This treatment protected against either acute or chronic ischemic brain injury. Remarkably, these effects of carfilzomib were abolished in <i>bnip3l</i><sup>-/-</sup> mice. Taken together, the present study linked BNIP3L degradation by proteasomes with mitophagy deficiency in cerebral ischemia. We propose carfilzomib as a novel therapy to rescue ischemic brain injury by preventing BNIP3L degradation. <b>Abbreviations:</b> 3-MA: 3-methyladenine; AAV: adeno-associated virus; <i>ATG7</i>: autophagy related 7; BCL2L13: BCL2-like 13 (apoptosis facilitator); BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CFZ: carfilzomib; COX4I1: cytochrome c oxidase subunit 4I1; CQ: chloroquine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; I-R: ischemia-reperfusion; MAP1LC3A/LC3A: microtube-associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtube-associated protein 1 light chain 3 beta; O-R: oxygen and glucose deprivation-reperfusion; OGD: oxygen and glucose deprivation; PHB2: prohibitin 2; pMCAO: permanent middle cerebral artery occlusion; PRKN/PARK2: parkin RBR E3 ubiquitin protein ligase; PT: photothrombosis; SQSTM1: sequestosome 1; tMCAO: transient middle cerebral artery occlusion; TOMM20: translocase of outer mitochondrial membrane 20; TTC: 2,3,5-triphenyltetrazolium hydrochloride.
DOI: 10.6084/m9.figshare.12851429.v1
title: BNIP3L/NIX degradation leads to mitophagy deficiency in ischemic brains

description: Mitophagy, the elimination of damaged mitochondria through autophagy, promotes neuronal survival in cerebral ischemia. Previous studies found deficient mitophagy in ischemic neurons, but the mechanisms are still largely unknown. We determined that BNIP3L/NIX, a mitophagy receptor, was degraded by proteasomes, which led to mitophagy deficiency in both ischemic neurons and brains. BNIP3L exists as a monomer and homodimer in mammalian cells, but the effects of homodimer and monomer on mitophagy are unclear. Site-specific mutations in the transmembrane domain of BNIP3L (S195A and G203A) only formed the BNIP3L monomer and failed to induce mitophagy. Moreover, overexpression of wild-type BNIP3L, in contrast to the monomeric BNIP3L, rescued the mitophagy deficiency and protected against cerebral ischemic injury. The macroautophagy/autophagy inhibitor 3-MA and the proteasome inhibitor MG132 were used in cerebral ischemic brains to identify how BNIP3L was reduced. We found that MG132 blocked the loss of BNIP3L and subsequently promoted mitophagy in ischemic brains. In addition, the dimeric form of BNIP3L was more prone to be degraded than its monomeric form. Carfilzomib, a drug for multiple myeloma therapy that inhibits proteasomes, reversed the BNIP3L degradation and restored mitophagy in ischemic brains. This treatment protected against either acute or chronic ischemic brain injury. Remarkably, these effects of carfilzomib were abolished in <i>bnip3l</i><sup>-/-</sup> mice. Taken together, the present study linked BNIP3L degradation by proteasomes with mitophagy deficiency in cerebral ischemia. We propose carfilzomib as a novel therapy to rescue ischemic brain injury by preventing BNIP3L degradation. <b>Abbreviations:</b> 3-MA: 3-methyladenine; AAV: adeno-associated virus; <i>ATG7</i>: autophagy related 7; BCL2L13: BCL2-like 13 (apoptosis facilitator); BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; CFZ: carfilzomib; COX4I1: cytochrome c oxidase subunit 4I1; CQ: chloroquine; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; I-R: ischemia-reperfusion; MAP1LC3A/LC3A: microtube-associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtube-associated protein 1 light chain 3 beta; O-R: oxygen and glucose deprivation-reperfusion; OGD: oxygen and glucose deprivation; PHB2: prohibitin 2; pMCAO: permanent middle cerebral artery occlusion; PRKN/PARK2: parkin RBR E3 ubiquitin protein ligase; PT: photothrombosis; SQSTM1: sequestosome 1; tMCAO: transient middle cerebral artery occlusion; TOMM20: translocase of outer mitochondrial membrane 20; TTC: 2,3,5-triphenyltetrazolium hydrochloride.
DOI: 10.6084/m9.figshare.7608554
title: Additional file 4: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S4. List of 470 differentially expressed proteins in hybrid generations upon BPH infestation. (XLSX 38 kb)
DOI: 10.6084/m9.figshare.7608554.v1
title: Additional file 4: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S4. List of 470 differentially expressed proteins in hybrid generations upon BPH infestation. (XLSX 38 kb)
DOI: 10.6084/m9.figshare.12851438
title: HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation

description: Iron metabolism is involved in numerous physiological processes such as erythropoiesis, oxidative metabolism. However, the <i>in vivo</i> physiological functions of the iron metabolism-related gene <i>Hfe</i> in immune response during viral infection remain poorly understood. Here, we identified 5 iron metabolism-associated genes specifically affected during RNA virus infection by a high-throughput assay and further found that HFE was a key negative regulator of RIG-I-like receptors (RLR)-mediated type I interferons (IFNs) signaling. RNA virus infection inhibited the binding of HFE to MAVS (mitochondrial antiviral signaling protein) and blocked MAVS degradation via selective autophagy. HFE mediated MAVS autophagic degradation by binding to SQSTM1/p62. Depletion of <i>Hfe</i> abrogated the autophagic degradation of MAVS, leading to the stronger antiviral immune response. These findings established a novel regulatory role of selective autophagy in innate antiviral immune response by the iron metabolism-related gene <i>Hfe</i>. These data further provided insights into the crosstalk among iron metabolism, autophagy, and innate immune response. <b>Abbreviations:</b> ATG: autophagy-related; BAL: bronchoalveolar lavage fluid; BMDMs: bone marrow-derived macrophages; CGAS: cyclic GMP-AMP synthase; CQ: chloroquine; Dpi: days post-infection; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; HAMP: hepcidin antimicrobial peptide; Hpi: hours post-infection; HJV: hemojuvelin BMP co-receptor; IFNs: interferons; IL6: interleukin 6; IRF3: interferon regulatory factor 3; ISRE: interferon-stimulated response element; Lipo: clodronate liposomes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; MEFs: mouse embryonic fibroblasts; SLC40A1/FPN1: solute carrier family 40 (iron-regulated transporter), member 1; flatiron; SQSTM1/p62: sequestosome 1; STAT1: signal transducer and activator of transcription 1; STING1/STING: stimulator of interferon response cGAMP interactor 1; TBK1: TANK-binding kinase 1; TFRC/TfR1: transferrin receptor; TNF/TNFα: tumor necrosis factor; WT: wild type.
DOI: 10.6084/m9.figshare.12851438.v1
title: HFE inhibits type I IFNs signaling by targeting the SQSTM1-mediated MAVS autophagic degradation

description: Iron metabolism is involved in numerous physiological processes such as erythropoiesis, oxidative metabolism. However, the <i>in vivo</i> physiological functions of the iron metabolism-related gene <i>Hfe</i> in immune response during viral infection remain poorly understood. Here, we identified 5 iron metabolism-associated genes specifically affected during RNA virus infection by a high-throughput assay and further found that HFE was a key negative regulator of RIG-I-like receptors (RLR)-mediated type I interferons (IFNs) signaling. RNA virus infection inhibited the binding of HFE to MAVS (mitochondrial antiviral signaling protein) and blocked MAVS degradation via selective autophagy. HFE mediated MAVS autophagic degradation by binding to SQSTM1/p62. Depletion of <i>Hfe</i> abrogated the autophagic degradation of MAVS, leading to the stronger antiviral immune response. These findings established a novel regulatory role of selective autophagy in innate antiviral immune response by the iron metabolism-related gene <i>Hfe</i>. These data further provided insights into the crosstalk among iron metabolism, autophagy, and innate immune response. <b>Abbreviations:</b> ATG: autophagy-related; BAL: bronchoalveolar lavage fluid; BMDMs: bone marrow-derived macrophages; CGAS: cyclic GMP-AMP synthase; CQ: chloroquine; Dpi: days post-infection; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; HAMP: hepcidin antimicrobial peptide; Hpi: hours post-infection; HJV: hemojuvelin BMP co-receptor; IFNs: interferons; IL6: interleukin 6; IRF3: interferon regulatory factor 3; ISRE: interferon-stimulated response element; Lipo: clodronate liposomes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; MEFs: mouse embryonic fibroblasts; SLC40A1/FPN1: solute carrier family 40 (iron-regulated transporter), member 1; flatiron; SQSTM1/p62: sequestosome 1; STAT1: signal transducer and activator of transcription 1; STING1/STING: stimulator of interferon response cGAMP interactor 1; TBK1: TANK-binding kinase 1; TFRC/TfR1: transferrin receptor; TNF/TNFα: tumor necrosis factor; WT: wild type.
DOI: 10.6084/m9.figshare.7608557
title: Additional file 5: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S5. List of 59 differentially expressed proteins only in resistant cultivars after BPH infestation. (XLSX 24 kb)
DOI: 10.6084/m9.figshare.7608557.v1
title: Additional file 5: of Proteomic analysis of the rice (Oryza officinalis) provides clues on molecular tagging of proteins for brown planthopper resistance

description: Table S5. List of 59 differentially expressed proteins only in resistant cultivars after BPH infestation. (XLSX 24 kb)
DOI: 10.6084/m9.figshare.12851447.v1
title: Phosphorylation of ATG18a by BAK1 Suppresses Autophagy and Attenuates Plant Resistance against Necrotrophic Pathogens

description: Autophagy is critical for plant defense against necrotrophic pathogens, which causes serious yield loss on crops. However, the post-translational regulatory mechanisms of autophagy pathway in plant resistance against necrotrophs remain poorly understood. In this study, we report that phosphorylation modification on ATG18a, a key regulator of autophagosome formation in <i>Arabidopsis thaliana</i>, constitutes a post-translation regulation of autophagy, which attenuates plant resistance against necrotrophic pathogens. We found that phosphorylation of ATG18a suppresses autophagosome formation and its subsequent delivery into the vacuole, which results in reduced autophagy activity and compromised plant resistance against <i>Botrytis cinerea</i>. In contrast, overexpression of ATG18a dephosphorylation-mimic form increases the accumulation of autophagosomes and complements the plant resistance of <i>atg18a</i> mutant against <i>B. cinerea</i>. Moreover, BAK1, a key regulator in plant resistance, was identified to physically interact with and phosphorylate ATG18a. Mutation of <i>BAK1</i> blocks ATG18a phosphorylation at four of the five detected phosphorylation sites after <i>B. cinerea</i> infection and strongly activates autophagy, leading to enhanced resistance against <i>B. cinerea</i>. Collectively, the identification of functional phosphorylation sites on ATG18a and the corresponding kinase BAK1 unveiled how plant regulates autophagy during resistance against necrotrophic pathogens.
DOI: 10.6084/m9.figshare.7608590.v1
title: Additional file 1: of Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease

description: Table S1. A list of screened genes. (XLSX 18 kb)
DOI: 10.6084/m9.figshare.7608590
title: Additional file 1: of Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease

description: Table S1. A list of screened genes. (XLSX 18 kb)
DOI: 10.6084/m9.figshare.7608599
title: Additional file 3: of Proteomic analysis reveals response of differential wheat (Triticum aestivum L.) genotypes to oxygen deficiency stress

description: Table S1. The differentially expressed proteins (DEPs) (XLS 2273 kb)
DOI: 10.6084/m9.figshare.7608599.v1
title: Additional file 3: of Proteomic analysis reveals response of differential wheat (Triticum aestivum L.) genotypes to oxygen deficiency stress

description: Table S1. The differentially expressed proteins (DEPs) (XLS 2273 kb)