Molecular Phylogenetic Research Articles

Comparative analysis of chloroplast genomes reveals molecular evolution and phylogenetic relationships within the Papilionoideae of Fabaceae

BackgroundThe structure of chloroplast genomes (cpDNAs) in Fabaceae (Fab.) has undergone significant evolutionary modifications. Within the Papilionoideae (Pap.), the emergence of the Inverted Repeat-Lacking Clade (IRLC) represents a major genomic alteration. However, the molecular evolution and phylogenetic relationships within Pap. remain poorly resolved due to limited molecular data and incomplete research, highlighting the need for systematic investigation.PurposeThis study presents an in-depth analysis of the cpDNAs within the Pap., with the aim of unraveling the molecular evolution and phylogenetic interconnections among its species.MethodsComplete cpDNAs of 18 Pap. species were sequenced using the Illumina Novaseq 6000 platform, followed by assembly and annotation. Comparative genomic analyses were conducted to elucidate structural variations and phylogenetic relationships.ResultsThe research has uncovered significant differences in the structure and characteristics of the cpDNAs within the Pap.. The lengths of the cpDNAs of 18 species range from 121,190 bp to 158,539 bp, and they contain between 107 and 112 unique genes. Five species, namely Desmodium elegans and Indigofera bracteata, exhibit a typical quadripartite structure, while thirteen species from genera such as Astragalus (Ast.), Hedysarum (Hed.), and Caragana (Car.) are grouped within the Inverted Repeat-Lacking Clade (IRLC). Genetic characteristic analysis revealed a plentiful presence of SSR loci, with single-nucleotide repeats and dinucleotide (A/T) repeats being the most predominant. Notably, the cpDNAs of five species including D. elegans have experienced significant rearrangements. For example, an inversion of approximately 23 kilobase (kb) pairs was observed in Pueraria peduncularis and Sophora moorcroftiana. These species exhibit pronounced differences in their non-coding regions. Comparative genomic variations at cpDNA sites were identified. Moreover, by using D. elegans as a reference, six genes (ycf4, clpP, ycf1, trnI-GAU, accD, rpl32) displayed high nucleotide polymorphism (Pi > 0.1), and the Ka/Ks ratio for all protein-coding genes was determined to be less than 1. The topological structure of the constructed phylogenetic tree of 85 species was basically consistent with that of Pap.. Seven main clades were formed and relatively high bootstrap values were exhibited, further clarifying the evolutionary relationships among them.ConclusionThis study provides novel insights into the molecular evolution and phylogeny of Pap., offering a foundational resource for future taxonomic and evolutionary research.

Taenia asiatica: Mitochondrial signatures based analysis of an emerging public health threat in India.

Taenia asiatica is a zoonotic tapeworm, commonly known as Asian Taenia. It is an emerging sister species of T. saginata with pigs as intermediate hosts. The present study aimed at genetic characterization and population structure analysis of T. asiatica metacestodes in slaughtered pigs in Haryana, north India. In total, the vital organs of 253 slaughtered pigs were screened for the presence of T. asiatica metacestodes. The molecular identification and phylogenetics were performed targeting the mitochondrial NADH dehydrogenase subunit 1 (nad1) and cytochrome C oxidase subunit 1 (cox1) genes. The median-joining haplotype network and population structure analyses were performed with the sequences generated herein and GenBank-archived T. asiatica sequences for both mitochondrial signatures. Out of 253 pigs screened, the liver of only one animal showed the presence of T. asiatica metacestodes. The sequences generated herein exhibited 99.60% and 98.85% similarity to the GenBank-archived sequences of T. asiatica corresponding to the nad1 and cox1 genes, respectively. Overall, 2 and 6 haplotypes for the overall data set with low nucleotide (0.00399±0.00237 and 0.00095±0.00042) and low haplotype (0.400±0.237 and 0.131±0.054) diversities were recorded for the nad1 and cox1 genes, respectively. The negative values recorded for the neutrality indices exhibited deviations from neutrality and hence, propounded recent population expansion or purifying selection or selective sweep. The findings of the present study are of significant medical importance considering an emerging global public health threat of the neglected tapeworm T. asiatica.

Redescription and phylogeny of the little-known type species Rhinakis faurei Deroux, 1994 (Alveolata, Ciliophora, Nassophorea).

Ciliates of the class Nassophorea Small & Lynn, 1981, inhabit a wide range of aquatic environments and serve as a trophic link in microbial food webs. However, their diversity remains underestimated. In the present study, the morphology and molecular phylogeny of Rhinakis faurei Deroux, 1994, an insufficiently known nassulid ciliate, were investigated using an integrative taxonomic approach. The studied population was collected from a freshwater pond in Qingdao, China. Details of the live morphology and ciliature of R. faurei are documented for the first time, and an improved species diagnosis is provided. Phylogenetic analyses of the small subunit ribosomal RNA gene sequence revealed that R. faurei clusters within the family Nassulidae de Fromentel, 1874. However, evolutionary interrelationships within the Nassulidae remain obscure owing to under-sampling, the lack of sequence data for most nominal species, and low nodal support or unstable gene tree topologies.

Linking new DNA sequence data to old scientific names of Parvodinium (Peridiniopsidaceae, Dinophyceae)

ABSTRACT Parvodinium (Peridiniopsidaceae) comprises a fairly species-rich group of relatively small peridinialean dinophytes that differ only in inconspicuous traits. No DNA sequence information is available for many of these species, although such links are important for their unambiguous identification. We examined two species of Parvodinium using light and scanning electron microscopy. Sequences of the rRNA complex (including 32 new GenBank entries) were obtained and embedded in a representative taxon sample of Peridiniopsidaceae for molecular phylogenetics. Based on DNA sequence comparison the two species are closely related and comprise the sister group to Parvodinium marciniakii. The morphologies grossly matched the descriptions of Parvodinium dzieduszyckii and Parvodinium lubieniense, respectively, to which the studied materials are tentatively assigned. Our approach of integrative taxonomy provides links between morphologies and DNA sequences, filling the gaps in reference data bases that are essential in metabarcoding studies. Species of Parvodinium are not identifiable based on a single autapomorphy but rather based on a unique combination of traits. Developmental processes of both species, such as vegetative mitosis and sexual reproduction, appear similar to other species of Parvodinium, but life history of dinophytes remains understudied in general.

VEGFA Gene Expression in Breast Cancer Is Associated With Worse Prognosis, but Better Response to Chemotherapy and Immunotherapy.

Vascular endothelial growth factor-A (VEGFA) is a key inducer of angiogenesis, responsible for generating new blood vessels in the tumor microenvironment (TME) and facilitating metastasis. Notably, Avastin, which targets VEGFA, failed to demonstrate any significant benefit in clinical trials for breast cancer (BC). This study aimed to investigate the clinical relevance of VEGFA gene expression in BC. A total of 7,336 BC patients across eight independent cohorts: ISPY2 (GSE173839), Sweden Cancerome Analysis Network-Breast (SCAN-B) (GSE96058), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), GSE25066, GSE163882, GSE34138, GSE20194, and The Cancer Genome Atlas (TCGA), were analyzed. The calculated median VEGFA expression level was used to stratify these cohorts into high and low groups. High VEGFA was associated with worse disease-free, disease-specific, and overall survival in the METABRIC cohort, with findings supported by the SCAN-B cohort, which also showed worse overall survival (all P < 0.02). High VEGFA expression was seen in triple-negative breast cancer (TNBC) but not in BC with lymph node metastasis. Additionally, there was a significant correlation between high VEGFA expression and higher silent and non-silent mutations, single-nucleotide variant (SNV) neoantigens, homologous recombination defect, intratumoral heterogeneity, in the TCGA cohort. In the TCGA, METABRIC, and SCAN-B cohorts, high VEGFA BC was also associated with higher cell proliferation: higher Ki67 gene expression, higher Nottingham histological grade, and consistent enrichment of all the Hallmark cell proliferation-related gene sets. Unexpectedly, the angiogenesis gene set was not enriched in any of the cohorts and showed no association with infiltrations of lymphatic or blood vascular endothelial cells besides pericytes. High VEGFA BC had significantly less infiltration of anti-cancer immune cells but higher infiltration of pro-cancer immune cells in TCGA, METABRIC, and SCAN-B cohorts. Interestingly, BC, which had a pathological complete response (pCR) after anthracycline- and taxane-based neoadjuvant therapy, was associated with significantly heightened VEGFA expression in both estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- and TNBC subtypes in the GSE25066 cohort and after immunotherapy in ER+/ HER2- subtype, but not TNBC in the ISPY2 cohort. Our research indicates that high VEGFA BC confers high cell proliferation, reduced immune cell infiltration, and poorer survival, but allows better response to anthracycline- and taxane-based chemotherapy, and immunotherapy.

Molecular characterization of HER2-negative breast cancers reveals a distinct patient subgroup with 17q12 deletion and heterozygous loss of ERBB2.

The approval of trastuzumab deruxtecan has prompted the subgrouping of human epidermal growth factor receptor 2-negative (HER2-) breast cancers (BCs) to HER2 0 and HER2 low on the basis of immunohistochemistry, although the biological significance of these subgroups remains uncertain. This study is aimed to better understand the molecular and genetic differences among HER2- tumors stratified by quantitative levels of HER2. We analyzed the transcriptomic and genomic data from the Molecular Taxonomy of BC International Consortium (discovery cohort) and The Cancer Genome Atlas (independent validation cohort). HER2- BCs, including hormone receptor positive and triple negative, were divided into three subgroups based on ERBB2 messenger RNA (mRNA) levels: minimal, moderate and enhanced. We observed significant differences in mutational and transcriptional profiles across the subgroups. Tumors with enhanced ERBB2 mRNA expression had a higher prevalence of PIK3CA mutations and increased estrogen receptor signaling, while tumors with minimal ERBB2 mRNA expression displayed higher expression of proliferation and immune-related genes. We identified a distinct subgroup of BCs characterized by a large deletion of chromosome 17q12 (17q12del) with heterozygous loss of ERBB2, very low ERBB2 mRNA and HER2 protein expression. This subgroup was also enriched for heterozygous losses of TP53 and other tumor suppressor genes. Analysis of two large real-world cohorts of patients with HER2- metastatic BC (Dana-Farber Cancer Institute cohort n= 1063 and Memorial Sloan Kettering MetTropism cohort n= 1018) showed that patients with 17q12del and heterozygous loss of ERBB2 had poorer overall survival (OS). We identified a biologically and clinically distinct subgroup of BCs characterized by a 17q12del with a heterozygous loss of ERBB2 and low ERBB2 mRNA and HER2 protein expression. In two large real-world cohorts of patients with HER2- metastatic BC, this subgroup was associated with poor OS, highlighting its clinical significance.

New branch on the tree of life of Gastrotricha: establishment of a new genus for limno-terrestrial species

Abstract Gastrotricha encompass a diversity of free-living micrometazoans typically associated with aquatic or semi-aquatic environments. The discovery of a gastrotrich species in limno-terrestrial habitats challenges existing taxonomic classifications and expands our understanding of their ecological diversity. This study describes Dendroichthydium ibyrapora gen. et sp. nov., a new gastrotrich from epiphytic mosses found in Atlantic rainforest within Serra do Japi biological reserve, and establishes its taxonomic status through morphological and molecular analyses. Morphological characterization was conducted using light microscopy, scanning electron microscopy, and confocal laser scanning microscopy, revealing that D. ibyrapora exhibits distinctive adaptations suited to limno-terrestrial environments, including unique cuticular adaptations and rearrangement of locomotory cilia. Molecular phylogenetics, using 18S and 28S ribosomal DNA sequences, supports the recognition of Dendroichthydium as a new genus, distinctly separated from known genera within Paucitubulatina. Furthermore, we propose reclassifying Chaetonotus (Chaetonotus) silvaticus to Dendroichthydium silvaticus comb. nov. based on shared morphological traits. The establishment of the genus Dendroichthydium reflects the ongoing need to re-evaluate gastrotrich diversity and taxonomy, highlighting the role of underexplored limno-terrestrial habitats in hosting unique life forms. This study underscores the importance of integrating morphology and genetics to improve our understanding of phylogenetics and the evolutionary dynamics of Gastrotricha.

The evolution of wasp mimicry and biogeography in the genus Temnostoma (Diptera: Syrphidae).

One of the most remarkable examples of Batesian mimicry occurs in the genus Temnostoma Le Peletier & Audinet-Serville, 1828 (Diptera: Syrphidae). Adults of this genus have an overall resemblance to hymenopterans combined with behavioural mimicry (they move the fore legs in front of the head mimicking hymenopteran antennae). While some species of Temnostoma are considered highly accurate mimics of social wasps, other species have a darker colour pattern and are rather relatively poor yellowjacket mimics. Both colour phenotypes are widespread through the Holarctic. Here, we infer for the first time the evolutionary history of the genus with special focus on the evolution of mimicry and biogeography. With material covering 75 % of known species of Temnostoma and both colour phenotypes from each biogeographical region, we inferred a molecular phylogeny based on six molecular markers (mitochondrial protein-coding COI gene, nuclear 28 s rRNA gene, and four nuclear protein-coding genes: AATS, CK1, TULP, and RBP-15). Using Bayesian inference, we obtained a highly resolved phylogenetic tree supporting the monophyly of the genus Temnostoma as a sister group of genus Takaomyia Hervé-Bazin, 1914. Within Temnostoma, Te. daochus and Te. barberi (two Nearctic species with strikingly different mimicry patterns) were found to be closely related to each other and together form a lineage sister to the rest of the genus. Our results suggest that the behavioural mimicry of wasp antennae is a plesiomorphic state inherited from a common ancestor that includes the genera Temnostoma and Takaomyia. Within Temnostoma, the dark colour pattern (poor yellowjacket mimicry) appears to be an ancestral state and highly accurate social wasp mimicry has appeared two times independently within the genus. In some species inhabiting northern parts of the Holarctic, secondary darkening and consequent degradation of the yellowjacket mimicry appeared. This indicates high evolutionary plasticity and ongoing selection pressure on morphological characters related to mimicry in hover flies.

Molecular phylogeny and morphology reveal a new wood-inhabiting fungus, Hyphoderma cinereofuscum (Polyporales, Basidiomycota), from southwest China

Hyphoderma is one of the important representative groups of wood-inhabiting fungi. These fungi secrete various enzymes capable of degrading cellulose, hemicellulose, and lignin into simple inorganic substances. The taxa within the genus cause a white rot of wood, play a key role in the carbon cycle and are the most efficient wood decomposers in the forest ecosystem. This study proposes a new wood-inhabiting fungal taxon, Hyphoderma cinereofuscum, based on morphological features and molecular evidence. It is characterized by the white hymenial surface, a monomitic hyphal system, generative hyphae with simple-septa, colorless, thin-walled, the presence of the tubular and capitate cystidia, and cylindrical basidiospores 9–11.5 × 4.5–5 µm. The phylogenetic tree inferred from a combination of the internal transcribed spacer regions (ITS) and the large subunit nuclear ribosomal RNA gene (nLSU) revealed that Hyphoderma cinereofuscum nested in the Hyphoderma clade and is closely related to H. marginatum. A full description, illustrations and phylogenetic analysis results of the new species are provided.

Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone

BackgroundKlebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.MethodsOne hundred and one CG147 strains were sequenced and additional 911 publicly available CG147 genome sequences were included for analysis. The molecular epidemiology, population structure, and time phylogeny were investigated. The virulome, resistome, and mobilome were analyzed, and the recombination in the capsular region was studied. The CRISPR-Cas and anti-CRISPR were identified. The interplay between CRISPR-Cas, anti-CRISPR, and carbapenemase-encoding plasmids was analyzed and experimentally validated.ResultsWe analyzed 1012 global CG147 genomes, with 80.4% encoding at least one carbapenemase (NDM [529/1012, 52.3%], OXA-48-like [182/1012, 17.7%], and KPC [105/1012, 10.4%]). Surprisingly, almost all CG147 strains (99.7%, 1009/1,012) harbor a chromosomal type I-E CRISPR-Cas system, with 41.8% (423/1012) containing an additional plasmid-borne type IV-A3 CRISPR-Cas system, and both target IncF plasmids, e.g., the most prevalent KPC-encoding pKpQIL-like plasmids. We found the presence of IV-A3 CRISPR-Cas system showed a negative correlation with the presence of KPC. Interestingly, a prophage-encoding anti-CRISPR AcrIE8.1 and a plasmid-borne anti-CRISPR AcrIE9.2 were detected in 40.1% (406/1012) and 54.2% (548/1012) of strains, respectively, which displayed positive correlations with the presence of a carbapenemase. Plasmid transfer experiments confirmed that the I-E and IV-A3 CRISPR-Cas systems significantly decreased (p < 0.001) KPC-encoding pKpQIL plasmid conjugation frequencies, while the AcrIE8.1 and AcrIE9.2 significantly increased (p < 0.001) pKpQIL conjugation frequencies and protected plasmids from elimination by CRISPR-Cas I-E system.ConclusionsOur results indicated a complex interplay between CRISPR-Cas, anti-CRISPR, and mobile genetic elements that shape the evolution of CG147. Our findings advance the understanding of multi-drug resistance mechanisms and will aid in preventing the emergence of future MDR clones.

Sinocrassula holotricha (Crassulaceae), a new species from Sichuan, China

A new species of crassulacean acid metabolism, Sinocrassula holotricha, is described based on specimen collected from Sichuan Province, Southwest China. The new species can be distinguished from its morphologically and phylogenetically related species by the hairy plants and lack of rosette. In the present study, a molecular phylogeny, taxonomic description, distribution information, and photographs of this new species are presented.

Description of a new species of Prostheceraeus Schmarda, 1859 and redescription of a poorly known species, Phrikoceros sagamianus (Kato, 1937) comb. n., with inference of their phylogenetic positions within Pseudocerotoidea (Platyhelminthes: Polycladida: Cotylea)

ABSTRACT The superfamily Pseudocerotoidea Lang encompasses Euryleptidae Stimpson, Pseudocerotidae Lang, and Stylostomidae Dittman. These families include conspicuous, flamboyant marine flatworms with a worldwide distribution. Here, we describe a new euryleptid species belonging to Prostheceraeus Schmarda, 1859, based on specimens collected by dredging at depths of 100–180 m off Misaki, Japan. The new species, Prostheceraeus fragum sp. n., is distinguished by its unique dorsal colouration in that oval red maculae are radially distributed along the translucent cream body periphery. Additionally, based on newly collected topotypic specimens, we transfer the poorly known pseudocerotid species Pseudoceros sagamianus Kato, 1937, to the genus Phrikoceros Newman and Cannon, 1996. These specimens possess (1) a pharynx with shallow, simple folds, (2) a deeply ruffled body margin, and (3) ear-like pseudotentacles with folds. Our molecular phylogeny, based on partial 18S and 28S rDNA sequences, yielded two key findings: (1) Pr. fragum sp. n. nested within the clade containing all other Prostheceraeus species, and (2) Phrikoceros sagamianus comb. n. formed a clade with all other Phrikoceros and Monobiceros species, distinct from the Pseudoceros clade. These results support the generic affiliations established through our morphological examinations. Furthermore, based on the resulting phylogenetic trees, we discuss the systematics of Euryleptidae in relation to Stylostomidae. http://www.zoobank.org/urn:lsid:zoobank.org:pub:F4EA3E5D-F3E6-440E-AAD7-D75E17FA11AE

Leveraging survival analysis and machine learning for accurate prediction of breast cancer recurrence and metastasis

Breast cancer, with its high incidence and mortality globally, necessitates early prediction of local and distant recurrence to improve treatment outcomes. This study develops and validates predictive models for breast cancer recurrence and metastasis using Recurrence-Free Survival Analysis and machine learning techniques. We merged datasets from the Molecular Taxonomy of Breast Cancer International Consortium, Memorial Sloan Kettering Cancer Center, Duke University, and the SEER program, creating a comprehensive dataset of 272, 252 rows and 23 columns. Our methodology utilized three predictive strategies: assessing recurrence risk, differentiating local from distant recurrences, and identifying potential metastatic sites. Key prognostic factors were identified through survival analysis. LightGBM, XGBoost, and Random Forest models were employed and validated against data from the Baheya Foundation. The models demonstrated strong performance; the survival analysis achieved a C-index of 0.837. The LightGBM model reached an AUC of 92% in predicting recurrences, while XGBoost and Random Forest models distinguished recurrence types with up to 86% accuracy, and they effectively differentiated between bone metastasis and all other locations combined (brain, liver, and lungs). This study highlights the significant potential of machine learning in advancing breast cancer management and sets a new benchmark for predictive analytics. Future research will integrate genetic data to further enhance these models.

Deeper Insights into Species Diversity and Ecological Characterisation of the Macrosporum Group of the Genus Tuber

Tuber is a rare edible and medicinal fungus with a global distribution. The Macrosporum lineage within Tuber is a relatively small and infrequent clade, which has been receiving increasing attention due to the presence of an endangered species, T. gigantosporum. However, the species diversity, phylogenetic relationships, geographic distribution, and ecological characteristics of the Macrosporum group remain poorly understood. Through extensive sampling and combining the accurate and available global specimen and mycorrhizal data, 19 Tuber specimens from Southwest China were studied based on morphology, molecular systematics, and ecology. The specimens were identified as T. calosporum, T. glabrum, and T. sinomacrosporum within the Macrosporum group, with detailed descriptions provided, particularly supplementing the taxonomic features of T. glabrum. A classification key for the Macrosporum group species is also provided. The geographic distribution of specimens and diverse hosts suggest that the Macrosporum clade displays wider ecological adaptability. This study is important to better understand the diversity and conservation measures of Tuber resources throughout the world.

Revision of Entrophosporales, with Three Genera and an Identification Key for All Species Currently Attributed to This Order

The objective of the present study was to revise the recently described order Entrophosporales of the Glomeromycetes. The single family Entrophosporaceae had been divided into three genera, Entrophospora, Claroideoglomus and Albahypha, due to molecular phylogenetic or morphological analyses, but recently these three genera were combined within the type genus of the family, Entrophospora. Our new studies now suggest once more three genera, but Entrophospora and Claroideoglomus were not separated again. In the present study, we resurrected Albahypha with A. drummondii and A. furrazolae comb. nov. and established Alborhynchus gen. nov. with A. walkeri comb. nov. Morphologically, all glomoid morphs of the three genera have hyaline to white subtending hyphae with one spore wall continuous with the subtending hyphal wall. However, the genera can easily be differentiated from each other and from other glomoid species of the Glomeromycetes by the combination of the characteristics of the subtending hyphae, the staining reaction of the spore wall layers in Melzer’s reagent and phylogeny. In conclusion, the three AMF genera, currently recognized in the Entrophosporales, can unequivocally be identified by molecular phylogeny or by morphological characteristics of their spores and their subtending hyphae. An identification key distinguishes all AMF species currently attributed to Entrophosporales.

P1343 Impact of Biologic Therapy on Gut Microbiome in Crohn's Disease: An Indian Patient Cohort Study

Abstract Background The advent of biologic therapy has revolutionized the treatment paradigm in IBD. In developing countries including India, where affordability and accessibility drive the treatment choice, it is important to understand the mechanisms behind biologic therapy and pave way to the future to predict response rates. This prospective study examines the impact of biologic therapy on the gut microbiome in moderate-to severe CD patients in India. Methods Fecal samples were collected from healthy controls(n=36) and 39 CD patients at baseline and after completing induction doze [Infliximab (n=16), Vedolizumab (n=6), and Ustekinumab (n=17)]. Individuals on recent antibiotics(&amp;lt;8weeks)/probiotics/NSAIDs were excluded. Clinical response was assessed at 6-weeks, with follow-up at 6 months to classify responders (CDAI&amp;lt;150) and non-responders(CDAI&amp;gt;150). DNA was isolated from 114 fecal samples and subjected to whole-genome shotgun metagenomics to generate a minimum of 6GB data per sample. After removal of human DNA read contamination, taxonomy and functional annotation was assigned using Kraken2, Bracken, and Human3 tools and statistical significance by using Wilcoxon Test (R-Studio). Results The gut microbiome in CD at baseline exhibited reduced diversity, lower SCFA-producing bacteria and increased pro-inflammatory bacteria like Collinsella and Escherichia compared to healthy cohort. The human DNA content in fecal samples was significantly higher in CD compared to healthy cohort with mean of 19.2% and 0.06% respectively. Post biologic therapy, there was significant restoration of the gut microbiome with increase in bacterial diversity, increased abundance of SCFA-producing Firmicutes and Phascolaractobacterium , probiotic Bifidobacterium species and reduction in pathogenic bacteria Enterococcus gallinarium. The average human DNA content also decreased to 9.6%. On sub-analysis, between responders (n=31) and non-responders; pathogenic Klebsiella pneumonia, Fusobacterium and Corynebacterium were found to be higher in non-responders compared to responders (Fig2A). Further, 19 metabolic pathways significantly differed between responders and non-responders, which included those pathways responsible for degradation of carbohydrates and generation of precursor metabolites and energy higher in the former (Fig2B). Conclusion There is increased gut dysbiosis in CD relative to healthy cohort which appears to get restored upon biologic therapy. The findings suggest the biologic therapy may play a role in restoring the compromised intestinal barrier in CD. A microbiome-based signature to predict response rates on biologic therapy can be seen in future.

P0008 A multi-omics approach across multiple chronic inflammatory diseases identifies a distinct type-1-interferon endotype of Inflammatory Bowel Disease

Abstract Background IBD shares many clinical and immunological features with other chronic inflammatory diseases (CIDs) like rheumatoid arthritis (RA) and psoriasis (Pso). Extraintestinal manifestations, particularly in the joints and skin, often overlap with these CIDs. We hypothesize that a systems medicine approach involving omics-driven phenotyping of multiple CIDs can yield a novel, therapy-relevant molecular taxonomy of disease. In this study, we aim to identify IBD-specific molecular signatures and those shared with other CIDs, as well as novel endotypes of IBD. Methods We recruited a cross-sectional cohort of 650 patients with CIDs (CD, UC, RA, Pso, psoriatic arthritis [PsA], and systemic lupus erythematosus [SLE]) along with 202 healthy controls (HC) at the University Hospital Kiel. Active or inactive disease was defined by clinical activity scores (i.e., CD: CDAI &amp;lt;150; UC: partial Mayo ≤2). Blood samples were collected and subjected to RNA sequencing and methylation profiling. Detailed clinical phenotypes and 5 years-follow-up data were obtained by chart review. We conducted differential gene expression and methylation analyses comparing each CID with HCs to identify shared molecular signatures. Core (activity-independent) signatures were defined by the overlap of differential expression in both active vs. HC and inactive disease vs. HC. Biclustering methods (UnPaSt) were used to uncover distinct patient endotypes based on expression profiles. Results IBD shared the most differential signatures with RA, indicating common pathways in their pathogenesis. Core signatures upregulated across all CIDs correlated with DNA methylation changes, reflecting the molecular mechanism of chronicity, and were enriched in pathways related to cytokine signaling, neutrophil chemotaxis, and humoral immune response. While methylation signatures in enhancer regions were shared among most CIDs, disease-specific methylation was mainly located in CpG islands. One disease-overarching subgroup of 71 patients with active disease, identified by biclustering, exhibited upregulation of interleukin-27 and type-1 interferon signaling, including 16 out of 121 active IBD patients with a skewed sex ratio toward females and higher rates of therapy escalations within 5 years (Log-rank test: p=0.0089). Conclusion Our study highlights shared and disease-specific immune dysregulation pathways contributing to the pathogenesis of IBD and other CIDs. We show the clear presence of core signatures of disease regardless of disease activity, which could represent insights into actionable targets for causative treatments and better disease control of CIDs. With our approach, we identified a distinct molecular endotype of IBD with worse prognosis, warranting further validation studies. References This project has received funding from the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation", the BMBF (e:Med Network iTREAT 01ZX2202A), the European Union/Horizon2020 (SYSCID, No 733100) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR) and No 853995 (ImmUniverse).The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The content provided in this publication reflects the author's views only. Neither the Innovative Medicines Initiative (IMI JU) nor the European Commission are responsible for any use that may be made of the information it contains.

Exponential elliptic Sombor index of molecular trees

Exponential elliptic Sombor index of molecular trees

Cranial variation across spiny pocket mice (Heteromys, Liomys) in new phylogenetic and taxonomic perspectives.

Spiny pocket mice are usually divided into two genera, Heteromys and Liomys, and more recently the latter have been subsumed into the former, leaving subfamily Heteromyinae with one genus. However, this arrangement conveys false equivalency among heteromyines, and does not represent the great morphological, molecular, and ecological diversity in this subfamily. To address this, geometric morphometric methods were used to explore interspecific cranial variation in this subfamily, which were then evaluated in the context of recent phylogenetic and taxonomic findings. The dataset consisted of 65 landmarks on the crania of 328 adult voucher specimens (15 species, 114 localities). Allometry and habitat adaptation are potential explanations for some of the variation patterns. Morphometric clustering among some distant relatives suggests convergent adaptation to similar habitats. These results support recent taxonomic proposals for the subfamily based on molecular phylogenies, in which the three to four main lineages are assigned generic status. We summarize the evidence and describe their scaled cranial shape variation. These lineages consist of Heteromys as traditionally defined (i.e., not including Liomys) while the traditionally defined Liomys would be divided into the genera Schaeferia (S. adspersus + S. salvini), Liomys sensu stricto (L. irroratus), and potentially a fourth (new) undescribed/undiagnosed genus for L. pictus + L. spectabilis. The implications of the present study are that scaled cranial shape variation patterns align better with this modified taxonomy than earlier ones. Our results confirm the usefulness of geometric morphometrics in providing taxonomic insights in taxa that appear cryptic using traditional distance-based measurements.

Molecular phylogeny and biogeography of the genus Tulipa (Amana spp.) in East Asia.

The East Asian tulips (Amana spp.), which are endemic to East Asia, include the species A. edulis, recognized as the source of the traditional Chinese medicine (TCM) known as "Guangcigu." In this study, we collected 50 samples representing six Amana species: A. edulis, A. erythronioides, A. anhuiensis, A. kuocangshanica, A. wanzhensis, and A. baohuaensis, across China and sequenced their complete chloroplast genomes. Phylogenetic analyses based on 74 shared protein-coding sequences in the chloroplast genome, along with divergence time estimations and biogeographic studies, have yielded several key findings. First, Amana spp. is confirmed to be monophyletic, having originated in the Late Miocene approximately 95% confidence interval of 5.63-12.52 million years ago, with diversification occurring within the 95% confidence interval of 2.36-4.68 million years ago in the mid-Pliocene, primarily in the Anhui and Zhejiang provinces. Second, Amana spp. comprise six valid species, each exhibiting varying degrees of dispersal into adjacent regions. Third, A. edulis, which emerged in the mid-Pliocene, has significantly expanded its range, colonizing the western parts of Jiangsu, Henan, and Jiangxi provinces and extending into northeastern China, North Korea, and Japan. This broad distribution, in comparison to other Amana species, is likely attributable to the evolutionary effects of the East Asian monsoon climate, which was intensified by the uplift of the Qinghai-Tibet Plateau. Analysis of chloroplast DNA markers revealed notable differences between A. edulis and other species, providing a reliable method for identifying Guangcigu and ensuring the safe use of this TCM.