Proteogenomics and systems biology: quest for the ultimate missing parts

This review describes how intimately proteogenomics and system biology are imbricated. Quantitative cell-wide monitoring of cellular processes and the analysis of this information is the basis for systems biology. Establishing the most comprehensive protein-parts list is an essential prerequisite prior to analysis of the cell-wide dynamics of proteins, their post-translational modifications, their complex network interactions and interpretation of these data as a whole. High-quality genome annotation is, thus, a crucial basis. Proteogenomics consists of high-throughput identification and characterization of proteins by extra-large shotgun MS/MS approaches and the integration of these data with genomic data. Discovery of the remaining unannotated genes, defining translational start sites, listing signal peptide processing events and post-translational modifications, are tasks that can currently be carried out at a full-genomic scale as soon as the genomic sequence is available. Proteomics is increasingly being used at the primary stage of genome annotation and such an approach may become standard in the near future for genome projects. Advantageously, the same experimental proteomic datasets may be used to characterize the specific metabolic traits of the organism under study. Undoubtedly, comparative genomics will experience a renaissance taking into account this new dimension. Synthetic biology aimed at re-engineering living systems will also benefit from these significant progresses.     

Sorting nexin Snx41 is essential for conidiation and mediates glutathione-based antioxidant defense during invasive growth in Magnaporthe oryzae

The sorting nexins Atg20/Snx42 and Snx41 regulate membrane traffic and endosomal protein sorting and are essential for Cvt and/or pexophagy in yeast. Previously, we showed that macroautophagy is necessary for conidiation in the rice-blast fungus Magnaporthe oryzae. Here, we analyzed the physiological function(s) of selective autophagy in Magnaporthe through targeted deletion of MGG_12832, an ortholog of yeast SNX41 and ATG20/SNX42. Loss of MGG_12832 (hereafter SNX41) abolished conidia formation and pathogenesis in M. oryzae. Snx41-GFP localized as dynamic puncta or short tubules that are partially associated with autophagosomes and/or autophagic vacuoles. PX domain, but not macroautophagy per se, was required for such localization of Snx41-GFP in Magnaporthe. Although not required for nonselective autophagy, Snx41 was essential for pexophagy in Magnaporthe. We identified Oxp1, an ATP-dependent oxoprolinase in the gamma-glutamyl cycle, as a binding partner and potential retrieval target of Snx41-dependent protein sorting. The substrate of Oxp1, 5-oxoproline, could partially restore conidiation in the snx41Δ. Exogenous glutathione, a product of the gamma-glutamyl cycle, significantly restored pathogenicity in the snx41Δ mutant, likely through counteracting the oxidative stress imposed by the host. We propose that the gamma-glutamyl cycle and glutathione biosynthesis are subject to regulation by Snx41-dependent vesicular trafficking, and mediate antioxidant defense crucial for in planta growth and pathogenic differentiation of Magnaporthe at the onset of blast disease in rice.     

Comparative metabolomics implicates threitol as a fungal signal supporting colonization of Armillaria luteobubalina on eucalypt roots

Armillaria root rot is a fungal disease that affects a wide range of trees and crops around the world. Despite being a widespread disease, little is known about the plant molecular responses towards the pathogenic fungi at the early phase of their interaction. With recent research highlighting the vital roles of metabolites in plant root–microbe interactions, we sought to explore the presymbiotic metabolite responses of Eucalyptus grandis seedlings towards Armillaria luteobuablina, a necrotrophic pathogen native to Australia. Using a metabolite profiling approach, we have identified threitol as one of the key metabolite responses in E. grandis root tips specific to A. luteobubalina that were not induced by three other species of soil-borne microbes of different lifestyle strategies (a mutualist, a commensalist, and a hemi-biotrophic pathogen). Using isotope labelling, threitol detected in the Armillaria-treated root tips was found to be largely derived from the fungal pathogen. Exogenous application of d- threitol promoted microbial colonization of E. grandis and triggered hormonal responses in root cells. Together, our results support a role of threitol as an important metabolite signal during eucalypt-Armillaria interaction prior to infection thus advancing our mechanistic understanding on the earliest stage of Armillaria disease development. Comparative metabolomics of eucalypt roots interacting with a range of fungal lifestyles identified threitol enrichment as a specific characteristic of Armillaria pathogenesis. Our findings suggest that threitol acts as one of the earliest fungal signals promoting Armillaria colonization of roots.     

Immune-associated biomarkers for early diagnosis of Parkinson’s disease based on hematological lncRNA–mRNA co-expression

Early stage diagnosis of Parkinson’s disease (PD) is challenging without significant motor symptoms. The identification of effective molecular biomarkers as a hematological indication of PD may help improve the diagnostic timelines and accuracy. In the present paper, we analyzed and compared the blood samples of PD and control (CTR) patients to identify the disease-related changes and determine the putative biomarkers for PD diagnosis. Based on the RNA sequencing analysis, differentially expressed genes (DEGs) were identified, and the co-expression network of DEGs was constructed using the weighted gene correlation network analysis (WGCNA). The analysis leads to the identification of 87 genes that were exclusively regulated in the PD group, whereas 66 genes were significantly increased and 21 genes were significantly decreased in contrast with the control group. The results indicate that the core lncRNA–mRNA co-expression network greatly changes the immune response in PD patients. Specifically, the results showed that Prader Willi Angelman Region RNA6 (PWAR6), LINC00861, AC83843.1, IRF family, IFIT family and calcium/calmodulin-dependent protein kinase IV (CaMK4) may play important roles in the immune system of PD. Based on the findings from the present study, future research aims at identifying novel therapeutic strategies for PD.     

Rice yield formation under high day and night temperatures—A prerequisite to ensure future food security

Increasing temperatures resulting from climate change dramatically impact rice crop production in Asia. Depending on the specific stage of rice development, heat stress reduces tiller/panicle number, decreases grain number per plant and lower grain weight, thus negatively impacting yield formation. Hence improving rice crop tolerance to heat stress in terms of sustaining yield stability under high day temperature (HDT), high night temperature (HNT), or combined high day and night temperature (HDNT) will bolster future food security. In this review article, we highlight the phenological alterations caused by heat and the underlying molecular-physiological and genetic mechanisms operating under different types of heat conditions (HDT, HNT, and HDNT) to understand heat tolerance. Based on our synthesis of HDT, HNT, and HDNT effects on rice yield components, we outline future breeding strategies to contribute to sustained food security under climate change.