Development and validation of blood-based predictive biomarkers for response to PD-(L)-1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications.

Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICI) remain limited to a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetics and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveals a highly prevalent patient molecular profiles predictive of response to PD-(L)1 immune checkpoint inhibitors. A clinical blood test based on the set of 8 3D genomic biomarkers has been developed and validated on several independent cancer patient cohorts to predict response to PD-(L)1 immune checkpoint inhibition. The predictive 8 biomarker set is derived from prospective observational clinical trials, representing 229 treatments with Pembrolizumab, Atezolizumab, Durvalumab, in diverse indications: melanoma, non-small cell lung, urethral, hepatocellular, bladder, prostate cancer, head and neck, vulvar, colon, breast, bone, brain, lymphoma, larynx cancer, and cervix cancers. The 3D genomic 8 biomarker panel for response to immune checkpoint therapy achieved high accuracy up to 85%, sensitivity of 93% and specificity of 82%. This study demonstrates that a 3D genomic approach could be used to develop a predictive clinical assay for response to PD-(L)1 checkpoint inhibition in cancer patients.

Genomic architecture controls spatial structuring in Amazonian birds

Large rivers are ubiquitously invoked to explain the distributional limits and speciation of the Amazon Basin's mega-diversity. However, inferences on the spatial and temporal origins of Amazonian species have narrowly focused on evolutionary neutral models, ignoring the potential role of natural selection and intrinsic genomic processes known to produce heterogeneity in differentiation across the genome. To test how these factors may influence evolutionary inferences across multiple taxa, we sequenced whole genomes of populations for three bird species that co-occur in southeastern Amazonian and exhibit different life histories linked to their propensity to maintain gene flow across the landscape. We found that phylogenetic relationships within species and demographic parameters varied across the genome in predictable ways. Genetic diversity was positively associated with recombination rate and negatively associated with the species tree topology weight. Gene flow was less pervasive in regions of low recombination, making these windows more suitable for commonly used phylogenetic methods that assume a bifurcating-branching model. To corroborate that these associations were attributable to selection, we modeled the signature of adaptive alleles across the genome taking demographic history into account, and found that on average 31.6 percent of the genome showed high probability for patterns consistent with selective sweeps and linked selection directly affecting the estimation of evolutionary parameters. By implementing a comparative genomic approach we were able to disentangle the effects of intrinsic genomic characteristics and selection from the neutral processes and show how speciation hypotheses are sensitive to genomic architecture.

Enemy or ally: a genomic approach to elucidate the lifestyle of Phyllosticta citrichinaensis

Members of the fungal genus Phyllosticta can colonize a variety of plant hosts, including several Citrus species such as Citrus sinensis (orange), Citrus limon (lemon), and Citrus maxima (pomelo). Some Phyllosticta species have the capacity to cause disease, such as Citrus Black Spot, while others have only been observed as endophytes. Thus far, genomic differences underlying lifestyle adaptations of Phyllosticta species have not yet been studied. Furthermore, the lifestyle of Phyllosticta citrichinaensis is ambiguous, as it has been described as a weak pathogen but Kochs postulates may not have been established and the presence of this species was never reported to cause any crop or economic losses. Here, we examined the genomic differences between pathogenic and endophytic Phyllosticta spp. colonizing Citrus and specifically aimed to elucidate the lifestyle of Phyllosticta citrichinaensis. We found several genomic differences between species of different lifestyles, including groups of genes that were only present in pathogens or endophytes. We also observed that species, based on their carbohydrate active enzymes, group independent of their phylogenetic association, and this clustering correlated with trophy prediction. Phyllosticta citrichinaensis shows an intermediate lifestyle, sharing genomic and phenotypic attributes of both pathogens and endophytes. We thus present the first genomic comparison of multiple citrus-colonizing pathogens and endophytes of the genus Phyllosticta, and therefore provide the basis for further comparative studies into the lifestyle adaptations within this genus.

Genomic evidence of paternal genome elimination in globular springtails

Paternal genome elimination (PGE) - a type of reproduction in which males inherit but fail to pass on the genome of their father - evolved independently in six to eight arthropod clades. Thousands of species, including several important for agriculture, reproduce via this mode of reproduction. While some of the clades are well established PGE systems, the evidence in globular springtails (Symphypleona) remains elusive, even though they represent the oldest and most species rich clade putatively reproducing via PGE. We sequenced genomic DNA from whole bodies of Allacma fusca males with sufficiently high fractions (31 - 38%) of sperm to conclusively confirm that all the sperm carry one parental haplotype only. Although it is suggestive that the single haplotype present in sperm is maternally inherited, definitive genetic proof of the parent of origin is still needed. The genomic approach we developed allows for detection of genotypic differences between germline and soma in all species with sufficiently high fraction of germline in their bodies. This opens new opportunities for scans for reproductive modes in small animals.

Agrococcus massiliensis sp. nov., a Novel Bacterial Species Isolated from Human Healthy Skin

Marseille-Q4369 is a strain that we isolated from human healthy skin and characterized by taxono-genomic approach. Marseille-Q4369 exhibited 99.80% 16S rRNA sequence similarity with Agrococcus pavilionensisT the phylogenetically closest bacterium with standing in nomenclature. Furthermore, digital DNA–DNA hybridization revealed a maximum identity similarity of only 52.4% and an OrthoANI parameter provided a value of 93.63% between the novel organism and Agrococcus pavilionensisT. Marseille-Q4369 was observed to be a yellowish-pigmented, Gram-positive, coccoïd, facultative aerobic bacterium, and belonging to the Microbacteriaceae family. The major fatty acids detected are 12-methyl-tetradecanoic acid (66%), 14-methyl-hexadecanoic acid (24%) followed by 13-methyl-tetradecanoic acid (5%). The genome size of strain Marseille-Q4369 was 2,737,735-bp long with a 72,27 % G+C content. Taken altogether, these results confirm the status of this strain as a new member of the Agrococcus genus for which the name of Agrococcus massiliensis is proposed (=CSUR-Q4369 = DSM112404).

Comparative Genomic Analysis of Limosilactobacillus Pontis Reveals Genetic Characteristics of High GC Content and Potential Niches Adaptations

Limosilactobacillus pontis is a species of lactic acid bacteria (LAB) found in fermented milk, sourdough and broiler chickens gastrointestinal tract and so on. However, the evolutionary strategies and genomic characteristics of the species remain unknown, which limits its application. In this study, whole genome sequencing was combined with a comparative genomic approach to investigate genomic characteristics and evolutionary strategies of L. pontis; this includes three published genomic sequences and two strains isolated from fermented milk in Inner Mongolia, China. The mean genome size and GC content of L. pontis was 1.70 Mb and 53.06%, respectively. Within the LAB L. pontis has a high GC content. The phylogenetic tree based on 1,281 core genomes showed that strains from the same sources aggregated together in clusters. Genome information, average nucleotide identity values, and phylogenetic relationships amongst L. pontis from different sources indicated that strains have potential niche adaptability. Functional genomic aspects, GT2 and GT4 (glycosyltransferases, GTs) involved in the synthesis of cellulose and sucrose were the family with the largest number of carbohydrate enzymes in L. pontis, particularly strains isolated from fermented milk. It is worth mentioning that the ability of L. pontis to produce bacteriocin may increase its application potential. This study provides new insight into the genetic characteristics and potential niche adaptations of L. pontis.

Detecting Cd adaptation footprint in C. riparius with a multi-genomic approach

Evolutionary processes and acquired tolerance to toxicants are important factors governing how animals respond to chemical exposure. Evidence for increased tolerance to cadmium (Cd), a widely distributed toxic metal in aquatic environments, in Chironomus riparius is conflicting and still questioned if it happens through phenotypic plasticity or genetic adaptation. The present study considered the relevance of directional environmental changes by increasing contaminant concentration in a multigenerational selection experiment. Evaluation of measurable life-cycle traits, transcriptomic responses and quantitative genetics from an evolve and resequencing (E&R) experiment were integrated to assess the potential of C. riparius to adapt to Cd. Survival tests revealed some adaptation to Cd exposure. Genomic analyses showed a strong, genome-wide selective response in all replicates, emphasizing that even control laboratory conditions continually exert selective pressure. The integration of transcriptomic and genomic data could isolate the genes related to Cd acquired resistance. Those genes could be linked to an efflux of metals. Therefore, it is possible to conclude that C. riparius can endure long-term Cd exposure also through genetic adaptation.