Relating the gut metagenome and metatranscriptome to immunotherapy responses in melanoma patients.

BACKGROUND: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community. METHODS: In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression. RESULTS: Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p \u3c 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of L-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis. CONCLUSIONS: This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes

Improved annotation of the insect vector of citrus greening disease: Biocuration by a diverse genomics community

The Asian citrus psyllid (Diaphorina citri Kuwayama) is the insect vector of the bacterium Candidatus Liberibacter asiaticus (CLas), the pathogen associated with citrus Huanglongbing (HLB, citrus greening). HLB threatens citrus production worldwide. Suppression or reduction of the insect vector using chemical insecticides has been the primary method to inhibit the spread of citrus greening disease. Accurate structural and functional annotation of the Asian citrus psyllid genome, as well as a clear understanding of the interactions between the insect and CLas, are required for development of new molecular-based HLB control methods. A draft assembly of the D. citri genome has been generated and annotated with automated pipelines. However, knowledge transfer from well-curated reference genomes such as that of Drosophila melanogaster to newly sequenced ones is challenging due to the complexity and diversity of insect genomes. To identify and improve gene models as potential targets for pest control, we manually curated several gene families with a focus on genes that have key functional roles in D. citri biology and CLas interactions. This community effort produced 530 manually curated gene models across developmental, physiological, RNAi regulatory and immunity-related pathways. As previously shown in the pea aphid, RNAi machinery genes putatively involved in the microRNA pathway have been specifically duplicated. A comprehensive transcriptome enabled us to identify a number of gene families that are either missing or misassembled in the draft genome. In order to develop biocuration as a training experience, we included undergraduate and graduate students from multiple institutions, as well as experienced annotators from the insect genomics research community. The resulting gene set (OGS v1.0) combines both automatically predicted and manually curated gene models.Peer reviewedBiochemistry and Molecular BiologyEntomology and Plant Patholog

Annual program review, chemical pulping and bleaching, March 23-24, 1999.

"March 23-24, 1999."v. 1. Chemical fundamentals of bleaching: project F015 / Arthur J. Ragauskas, Lucian A. Lucia / Influence of Hexenuronic acids (HexA) on bleaching: project F015.1 / Art J. Ragauskas ; Oxalic acid process chemistry: project F015.2 / Art J. Ragauskas ; High efficiency peroxide bleaching: project F015.3 / Art J. Ragauskas ; Laccase-mediator bleaching of kraft pulp: project F014.4 / Art J. Ragauskas ; Oxygen delignification: project F015.5 / Lucian A. Lucia ; Environmentally compatible production of bleached pulp / T.J. McDonough ... [et al.] ; Environmentally compatible production of bleached chemical pulp: project F013 ; Partial substitution of ozone for chlorine dioxide in the first stage of softwood kraft pulp bleaching sequences / T.J. McDonough , M. Turner , and C.E. Courchene ; Partial substitution of ozone for chlorine dioxide in the first stage of hardwood kraft pulp bleaching sequences / T.J. McDonough , A. Shaker , and C.E. Courchene ; Effects of digester conditions on the bleachability of southern pine kraft pulp / T.J. McDonough , A.J. Bacon , and M. Turner ; Hydrogen peroxide delignification of softwood kraft brownstock / T.J. McDonough , C.E. Courchene , and M. Alger ; Effects of pulping and bleaching processes on pulp and fiber properties / C. Courchene ... [et al.] -- v. 2. High strength, high yield bleached pulps: project F030 / J. Li ... [et al.] ; How much should the yield of softwood chemical pulp (kraft pulp) be improved? Limitations from physical strength / Jian Li ; Nonuniformity of carbohydrate degradation during kraft pulping-measurement and modeling using a modified g-factor / Jian Li , Geoff Moeser , Laura Rosen ; Closed mill-metals equilibria: project F017 / Alan Rudie ; Fundamentals of brightness reverstion: project F014 / Art J. Ragauskas ; Lignin reactivity during pulping and bleaching: project 4226 / Donald Dimmel , John MacKay ; Trees containing built-in pulping cataylst: project 4181 / Donald Dimmel ... [et al.] ; Improved selectivity in ozone bleaching: project 4168 / Donald Dimmel , Perla Sklar , Elizabeth Althen ; Metals management in low effluent pulp and paper mills: project 4192 / Alan Rudie -- Slide Material

Annual program review, forest biology

"March 25-26, 1999."Mass clonal propagation of improved conifers: status report for project F010 / Gerald Pullman ... [et al.] ; Mass clonal propagation of improved conifers - initiation / Gerald Pullman ... [et al.] ; Variation in initiation and the number of zygotic embryos in the seed / John MacKay ... [et al.] ; Survival of initiated cultures after direct transfer into liquid media: the effect of maltose, auxin type, and genotype / Gary Peter , Teresa Vales ; Embryo development improvements based on elemental analysis of female gametophyte, zygotic and somatic embryo tissues / Gerald Pullman , Paul Montello , Xiaorong Feng ; Optimizing the percent of embryos that develop into cotyledonary embryos: the role of plating density and ABA concentration / Gary Peter , Teresa Vales ; Field establishment of somatic embryo derived loblolly pine seedlings / Jerry Pullman , Paul Montello , Mike Cunningham ; Analysis of free amino acids, nitrate, and ammonium in zygotic female gametophyte and embryo tissues / Gerald Pullman ... [et al.] ; Functional analysis of pinus taeda zygotic embryo germination: the effect of partial drying and the acquisition of desiccation tolerance / Gary Peter ... [et al.] ; Gene expression in pine embryos; developing tools / John Cairney , Gerald Pullman , John MacKay ; Differential gene expression in the suspensor of zygotic embryos / John MacKay ... [et al.] ; Analysis of a late stage-specific clone of loblolly pine by a non-radioactive method of cDNA labeling and detection / Barbara Johns and John Cairney ; Externally funded research in 1998-1999 supporting F010 / John Cairney ... [et al.] ; Developing reliable systems for evaluating gene expression using DNA arrays / Lin Ge , Jerry Pullman and John Cairney ; Early-specific gene expression in loblolly pine zygotic and somatic embryos: cDNS cloning, sequencing and expression analysis / Vincent Ciavatta , Gerald Pullman , John Cairney ; Fundamental biological mechanisms: improved stem growth rates and fiber properties: status reports for project F011 / Gary Peter ... [et al.] ; Externally funded research in 1998-1999 supporting F011 / Gary Peter ... [et al.] ; Transformation methods for southern pine: building an efficient transformation method for loblolly pine / Gary Peter ... [et al.] ; Environmental and genetic regulation of microfibril angle in southern pine: determination of the microfibril angle in the s2 layer of pinus taeda using differential interference contrast microscopy: validation of the method / Douglas Benton , Keith Bennett , Gary Peter ; Trees containing built-in pulping catalysts / Jerry Pullman ... [et al.] ; Lignin reactivity during pulping and bleaching of CAD-deficient pine / John MacKay ... [et al.] ; IPST forest biology research proposals ; Student research -- Slide Material