Complex Patterns Of Evolution Research Articles

A Review on Bridging Molecular Biology and Ecological Dynamics through Integrative Approaches in Zoology

The integration of molecular biology with ecological dynamics has emerged as a transformative approach in zoology, enhancing our understanding of biodiversity, ecosystem health, and the adaptive responses of species to environmental changes. This review synthesizes key developments and methodological innovations at the intersection of molecular biology and ecological dynamics, highlighting the application of DNA barcoding, environmental DNA (eDNA) analyses, molecular phylogenetics, and advanced computational models in elucidating complex biological interactions and evolutionary patterns. Significant advancements include the use of high-throughput sequencing technologies and CRISPR-Cas systems that have expanded our ability to explore genetic diversity and manipulate genetic material for conservation purposes. The review discusses the predictive capabilities of integrative models that combine genetic with ecological data, offering insights into species resilience and ecosystem stability under varying environmental scenarios. Challenges in data integration, such as issues of scale, complexity, and the necessity for interdisciplinary cooperation, are critically examined. Technical limitations related to data management and ethical considerations in the use of genetic information are also explored. Looking forward, the review identifies emerging technologies and their potential impacts on ecological and conservation biology, emphasizing the need for policies that support sustainable management and conservation strategies. This review underscores the profound impact of integrating molecular biology with ecological dynamics, which not only enhances our scientific understanding but also provides practical frameworks for addressing global environmental challenges.

Museum skins enable identification of introgression associated with cytonuclear discordance.

Increased sampling of genomes and populations across closely related species has revealed that levels of genetic exchange during and after speciation are higher than previously thought. One obvious manifestation of such exchange is strong cytonuclear discordance, where the divergence in mitochondrial DNA (mtDNA) differs from that for nuclear genes more (or less) than expected from differences between mtDNA and nuclear DNA (nDNA) in population size and mutation rate. Given genome-scale datasets and coalescent modelling, we can now confidently identify cases of strong discordance and test specifically for historical or recent introgression as the cause. Using population sampling, combining exon capture data from historical museum specimens and recently collected tissues we showcase how genomic tools can resolve complex evolutionary histories in the brachyotis group of rock-wallabies (Petrogale). In particular, applying population and phylogenomic approaches we can assess the role of demographic processes in driving complex evolutionary patterns and assess a role of ancient introgression and hybridisation. We find that described species are well supported as monophyletic taxa for nDNA genes, but not for mtDNA, with cytonuclear discordance involving at least four operational taxonomic units (OTUs) across four species which diverged 183-278 kya. ABC modelling of nDNA gene trees supports introgression during or after speciation for some taxon pairs with cytonuclear discordance. Given substantial differences in body size between the species involved, this evidence for gene flow is surprising. Heterogenous patterns of introgression were identified but do not appear to be associated with chromosome differences between species. These and previous results suggest that dynamic past climates across the monsoonal tropics could have promoted reticulation among related species.

Link prediction by continuous spatiotemporal representation via neural differential equations

With the continuous advancement of data science and machine learning, temporal link prediction has emerged as a crucial aspect of dynamic network analysis, providing significant research and application potential across various domains. While deep learning techniques have achieved remarkable results in temporal link prediction, most existing studies have focused on discrete model frameworks. These frameworks face limitations in capturing deep structural features and effectively aggregating temporal information. To address these limitations, we draw inspiration from neural differential equations to propose a Continuous Temporal Graph Neural Differential Equation (CTGNDE) network model for temporal link prediction. Specifically, we design a spatial graph Ordinary Differential Equation (ODE) to capture the spatial correlations inherent in complex spatiotemporal information. Then we employ Neural Controlled Differential Equation (Neural CDE) to learn complex evolution patterns and effectively aggregate temporal information. Finally, we characterize completely continuous and more accurate hidden state trajectories by coupling spatial and temporal messages. Experiments conducted on 10 real-world network datasets validated the superior performance of the CTGNDE model over the state-of-the-art baselines.

Unveiling the Genetic Tapestry: Exploring Rhizoctonia solani AG-3 Anastomosis Groups in Potato Crops across Borders.

The current study was carried out to screen 10 isolates (ARS-01-ARS-10) of Rhizoctonia. solani from potato tubers cv. Kuroda, which were collected from various potato fields in Multan, Pakistan. The isolates were found to be morphologically identical, as the hyphae exhibit the production of branches at right angles and acute angles often accompanied by septum near the emerging branches. Anastomosis grouping showed that these isolates belonged to AG-3. A pathogenicity test was performed against the susceptible Kuroda variety and among the isolates, ARS-05 exhibited the highest mean severity score of approximately 5.43, followed by ARS-09, which showed a mean severity score of about 3.67, indicating a moderate level of severity. On the lower end of the severity scale, isolates ARS-06 and ARS-07 displayed mean severity scores of approximately 0.53 and 0.57, respectively, suggesting minimal symptom severity. These mean severity scores offer insights into the varying degrees of symptom expression among the different isolates of R. solani under examination. PCoA indicates that the severe isolate causing black scurf on the Kuroda variety was AG-3. A comprehensive analysis of the distribution, genetic variability, and phylogenetic relationships of R. solani anastomosis groups (AGs) related to potato crops across diverse geographic regions was also performed to examine AG prevalence in various countries. AG-3 was identified as the most widespread group, prevalent in Sweden, China, and the USA. AG-5 showed prominence in Sweden and the USA, while AG-2-1 exhibited prevalence in China and Japan. The phylogenetic analysis unveiled two different clades: Clade I comprising AG-3 and Clade II encompassing AG-2, AG-4, and AG-5, further subdivided into three subclades. Although AGs clustered together regardless of origin, their genetic diversity revealed complex evolutionary patterns. The findings pave the way for region-specific disease management strategies to combat R. solani's impact on potato crops.

Geomorphology and Age Constraints of Seamounts in the Cabo Verde Archipelago, and Their Relationship to Island Ages and Geodynamic Evolution

AbstractThe Cabo Verde Archipelago is related to a mantle plume located close to the rotational pole of the African Plate. It consists of islands and seamounts arranged in a horseshoe‐shaped pattern open to the west, thus forming two volcanic chains, each with a weak east‐west age progression. High‐resolution swath bathymetry of 12 Cabo Verde seamounts is used here to assign each seamount to its pre‐shield, shield or post‐shield evolutionary stage, respectively. The eastern seamounts exhibit degraded and partially eroded morphologies, and are mainly in their post‐shield stage. A new 40Ar‐39Ar date for Senghor Seamount at 14.872 ± 0.027 Ma supports old ages for the eastern seamounts. The western seamounts generally exhibit younger volcanic‐edifice‐construction morphologies, showing fresh effusive and explosive volcanics, including rarely observed deep‐water explosive volcanism in the Charles Darwin Volcanic Field. Furthermore, the two previously unknown seamounts Sodade and Tavares in the westernmost termini of both volcanic chains exhibit pristine volcanic morphologies, in agreement with present‐day volcanism and seismic activity recorded from the western seamounts. The islands and seamounts rest on three submarine platforms to the east, northwest and southwest, respectively. Taken together, the seamount and island data suggest a shift in igneous activity from the eastern to the other platforms at about 8–6 Ma. However, the complex evolution pattern for both volcanic chains includes the simultaneous occurrence of pre‐shield or shield edifices at any time, followed by erosional and rejuvenation stages. The new seamount data still demonstrate ongoing westward submarine‐growth in both volcanic chains.

Phylogenomic discernments into Anaerolineaceae thermal adaptations and the proposal of a candidate genus Mesolinea.

This study delves into the evolutionary history of Anaerolineaceae, a diverse bacterial family within the Chloroflexota phylum. Employing a multi-faceted approach, including phylogenetic analyses, genomic comparisons, and exploration of adaptive features, the research unveils novel insights into the family's taxonomy and evolutionary dynamics. The investigation employs metagenome-assembled genomes (MAGs), emphasizing their prevalence in anaerobic environments. Notably, a novel mesophilic lineage, tentatively named Mesolinea, emerges within Anaerolineaceae, showcasing a distinctive genomic profile and apparent adaptation to a mesophilic lifestyle. The comprehensive genomic analyses shed light on the family's complex evolutionary patterns, including the conservation of key operons in thermophiles, providing a foundation for understanding the diverse ecological roles and adaptive strategies of Anaerolineaceae members.

Bi-DNE: bilayer evolutionary pattern preserved embedding for dynamic networks

AbstractNetwork embedding is a technique used to generate low-dimensional vectors representing each node in a network while maintaining the original topology and properties of the network. This technology enables a wide range of learning tasks, including node classification and link prediction. However, the current landscape of network embedding approaches predominantly revolves around static networks, neglecting the dynamic nature that characterizes real social networks. Dynamics at both the micro- and macrolevels are fundamental drivers of network evolution. Microlevel dynamics provide a detailed account of the network topology formation process, while macrolevel dynamics reveal the evolutionary trends of the network. Despite recent dynamic network embedding efforts, a few approaches accurately capture the evolution patterns of nodes at the microlevel or effectively preserve the crucial dynamics of both layers. Our study introduces a novel method for embedding networks, i.e., bilayer evolutionary pattern-preserving embedding for dynamic networks (Bi-DNE), that preserves the evolutionary patterns at both the micro- and macrolevels. The model utilizes strengthened triadic closure to represent the network structure formation process at the microlevel, while a dynamic equation constrains the network structure to adhere to the densification power-law evolution pattern at the macrolevel. The proposed Bi-DNE model exhibits significant performance improvements across a range of tasks, including link prediction, reconstruction, and temporal link analysis. These improvements are demonstrated through comprehensive experiments carried out on both simulated and real-world dynamic network datasets. The consistently superior results to those of the state-of-the-art methods provide empirical evidence for the effectiveness of Bi-DNE in capturing complex evolutionary patterns and learning high-quality node representations. These findings validate the methodological innovations presented in this work and mark valuable progress in the emerging field of dynamic network representation learning. Further exploration demonstrates that Bi-DNE is sensitive to the analysis task parameters, leading to a more accurate representation of the natural evolution process during dynamic network embedding.

A comprehensive phylogenomic study unveils evolutionary patterns and challenges in the mitochondrial genomes of Carcharhiniformes: A focus on Triakidae

The complex evolutionary patterns in the mitochondrial genome (mitogenome) of the most species-rich shark order, the Carcharhiniformes (ground sharks) has led to challenges in the phylogenomic reconstruction of the families and genera belonging to the order, particularly the family Triakidae (houndsharks). The current state of Triakidae phylogeny remains controversial, with arguments for both monophyly and paraphyly within the family. We hypothesize that this variability is triggered by the selection of different a priori partitioning schemes to account for site and gene heterogeneity within the mitogenome. Here we used an extensive statistical framework to select the a priori partitioning scheme for inference of the mitochondrial phylogenomic relationships within Carcharhiniformes, tested site heterogeneous CAT + GTR + G4 models and incorporated the multi-species coalescent model (MSCM) into our analyses to account for the influence of gene tree discordance on species tree inference. We included five newly assembled houndshark mitogenomes to increase resolution of Triakidae. During the assembly procedure, we uncovered a 714 bp-duplication in the mitogenome of Galeorhinus galeus. Phylogenetic reconstruction confirmed monophyly within Triakidae and the existence of two distinct clades of the expanded Mustelus genus. The latter alludes to potential evolutionary reversal of reproductive mode from placental to aplacental, suggesting that reproductive mode has played a role in the trajectory of adaptive divergence. These new sequences have the potential to contribute to population genomic investigations, species phylogeography delineation, environmental DNA metabarcoding databases and, ultimately, improved conservation strategies for these ecologically and economically important species.

A deep marked graph process model for citywide traffic congestion forecasting

AbstractForecasting citywide traffic congestion on large road networks has long been a nontrivial research problem due to the challenge of modeling complex evolution patterns of congestion in highly stochastic traffic environments. Arguing that purely data‐driven methods may not perform well for congestion forecasting, we propose a deep marked graph process model for predicting the congestion indices and the occurrence time of traffic congestion events for complex signalized road networks. Traffic congestion is considered as a nonrigorous spatiotemporal extreme event. We extend the traditional point process model by integrating a specially designed spatiotemporal graph convolutional network. This hybrid strategy takes advantage of the simple form of the point process model as well as the ability of graph neural networks to emulate the evolution of congestion. Experiments on real‐world congestion data sets show that the proposed method outperforms state‐of‐the‐art baseline methods, yielding satisfactory prediction results on a large signalized road network with superior computational efficiency.

RetroSeeker reveals the characteristics, expression, and evolution of a large set of novel retrotransposons

Retrotransposons are highly prevalent in most animals and account for more than 35% of the human genome. However, the prevalence, biogenesis mechanism and function of retrotransposons remain largely unknown. Here, we developed retroSeeker, a novel computational software that identifies novel retrotransposons from pairwise alignments of genomes and decodes their biogenesis, expression, evolution and potential functions. We discovered that the majority of new retrotransposons exhibit a specific L1 endonuclease cleavage motif, with some motifs precisely located ten nucleotides upstream of the insertion site. We identified that a large number of candidate functional genes might be generated through a retrotransposition mechanism. Importantly, we uncovered previously uncharacterized classes of retrotransposons related to histone genes, mitochondrial genes and vault RNAs. Moreover, we elucidated the tissue-specific expression of retrotransposons and demonstrated their ubiquitous expression in various cancer types. We also revealed the complex evolutionary patterns of retrotransposons and identified numerous species-specific retrotransposition events. Taken together, our findings establish a paradigm for discovering novel classes of retrotransposons and elucidating their new characteristics in any species.

Genomic analysis of two rare human G3P[9] rotavirus strains in Ningxia, China

G3P (Matthijnssens et al., 2008b [9]) is a rare combination of human rotavirus VP7/VP4 genotypes with a complex evolutionary pattern but limited related studies. Detailed genomic characterisation and genetic evolutionary analyses of G3P (Matthijnssens et al., 2008b [9]) rotaviruses have helped to enhance our understanding of rotavirus diversity. For the first time, we detected two human G3P (Matthijnssens et al., 2008b [9]) Rotavirus A (RVA) strains, RVA/Human-tc/CHN/2020999/2020/G3P (Matthijnssens et al., 2008b [9]) and RVA/Human-wt/CHN/23582009/2023/G3P (Matthijnssens et al., 2008b [9]), in diarrhoea patients from the Ningxia region of China, and carried out a whole-genome analysis of these strains. 2,020,999 and 23,582,009 have identical gene constellations: G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3, and this genotypic constellation was reported first time in China. They are closely related in 11 genome segments. The genotypes of these two strains are different from the human RVA strains L621 and E2451, which are only G3P (Matthijnssens et al., 2008b [9]) strains reported so far in China, but are identical to those of the Thai feline strain Meesuk and the Korean human strain CAU12–2-51.Phylogenetic analysis showed that the VP6, VP1-VP3, and NSP2 genes of the two strains in this study clustered with human/bovine and feline/bovine rotavirus strains to form a sublineage distinct from the common DS-1-like G2 human rotavirus. In contrast, the VP7, VP4, NSP1, and NSP3-NSP5 gene segments were closely associated with human/feline rotavirus and feline rotavirus strains. These findings suggest that the evolutionary origin of the G3P (Matthijnssens et al., 2008b [9]) human rotavirus found in Ningxia, China, is consistent with the Meesuk and CAU12–2-51 strains， may have arisen through reassortment between uncommon human/bovine， feline/bovine rotavirus strains and human/feline， feline rotaviruses. However, VP1-VP2 gene segments did not have the same lineage as strains Meesuk and CAU12–2-51, suggesting that these genes might be derived from additional reassortment event.

Palaeobiogeography of NE Atlantic archipelagos during the last Interglacial (MIS 5e): A molluscan approach to the conundrum of Macaronesia as a marine biogeographic unit

In order to understand the complex evolutionary processes and patterns that explain current island biodiversity, large datasets and long-term analysis are required. The Last Interglacial (LIG) was one of the warmest interglacials during the last million years. How species mobility changed during this period in the Macaronesia geographical region has long intrigued scientists. It is well established that the northward range expansion of tropical species occurred in the Macaronesian geographical region, but as a marine biogeographic unit, the term “Macaronesia” has not gained a consensus among the scientific community. For the first time, a thoroughly revised and updated checklist is presented for shallow-water marine molluscs from the Atlantic and Mediterranean during the LIG. Based on these wide ranging data, the status of Macaronesia as a marine biogeographic unit during the LIG was examined and our scientific understanding of how this unit evolved is improved. The analysis shows that during the LIG, the molluscan faunas of the Canary and Cabo Verde archipelagos were part of the same tropical Late Pleistocene Mediterranean West-African Province, whereas those in the Azores, Madeira and Selvagens archipelagos would be included in the subtropical Late Pleistocene French-Iberian Province. This contrasts with the present-day scenario, where the subtropical/warm temperate Azores and “Webbnesia” marine ecoregions (Lusitanian province) are biogeographically distinct from the Cabo Verde biogeographic subprovince, which in turn belongs to the West African Tropical biogeographic province. A further analysis of the coherence of “Macaronesia” as a marine biogeographical unit was accomplished by coupling Pliocene, LIG, and present-day data, showing that the term “Macaronesia”, and for the marine realm, should only be used in a geographical connotation.

Niche evolution and diversification in Middle Eastern stream salamanders (Paradactylodon): vulnerability to future climate change

Abstract The relict genus Paradactylodon is narrowly distributed in temperate forests throughout the Middle East region, including P. mustersi in Afghanistan, P. persicus, and P. gorganensis in northwestern and northeastern Iran. Recent phylogenetic analyses suggest that the Iranian Paradactylodon populations may belong to a single species, P. persicus. In this study, we addressed how climatic niche conservatism and/or niche divergence may have affected the evolution of all Paradactylodon species using ecological niche models and multivariate niche analyses to identify niche overlap and assess equivalency and similarity tests. We also used an ensemble of ten algorithms to predict Paradactylodon species distributions for recent (1970-2000) and future (2081-2100) climate conditions. The results show that future climate change may cause the loss of 80 to 97% of these species’ suitable habitat, especially at lower elevations. The niche divergence hypothesis was supported by the results of niche equivalency tests on P. persicus vs. P. gorganensis (and vice versa) with moderate overlap (D = 0.23, I = 0.41) and P. persicus vs. P. mustersi (and vice versa) with little overlap (D = 0.05, I = 0.06). Meanwhile, the niche similarity test for the niche conservatism hypothesis revealed significant results for P. persicus vs. P. gorganensis, P. mustersi vs. P. persicus, and P. persicus + P. gorganensis (as a single species) vs. P. mustersi. Due to these complex evolutionary ecological patterns and allopatric distributions, we recommend that P. gorganensis be considered a valid subspecies.

The role of in-channel vegetation in driving and controlling the geomorphic changes along a gravel-bed river

Gravel-bed rivers are fluvial systems featuring highly complex morphological and evolutionary patterns because of their configuration characterized by the contemporary presence of many distinct morphological units. Complexity can also be observed in the response of gravel-bed rivers to flow conditions, which can be highly varied. This work aims to analyze the evolution of gravel and vegetated areas in a gravel-bed river during a period of persistent low flow conditions, focusing also on the responses exhibited by the different types of riparian vegetation. To this end, a 2200 m-long segment of the Piave River (NE Italy) was considered. It was surveyed twice by LiDAR (August 2003 and August 2010), permitting the analysis of the spatial-temporal evolution of gravel and vegetated areas through both cover type analysis and the DoD technique. During the study period (August 2003 – August 2010), the flow conditions were constantly ordinary, i.e., under-bankfull. The cover type analysis stressed an increase of +115 % in vegetated areas, which have diffusely colonized the river corridor. However, the low flow conditions also induced geomorphic changes with 54 % of the study area affected by variations in surface elevation. The DoD computed a diffuse deposition over the main and secondary channels, while erosion was observed in specific areas of the main fluvial island and along the right floodplain. In terms of vegetation changes, five eroded patches were identified, which contributed to 60 % of the vegetated area entirely eroded in the study reach. These patches were mainly characterized by mature vegetation taller than the mean vegetation height observed over the study reach. Therefore, the analysis of the response of the Piave River to persistent under-bankfull flows stressed a complex evolution of the gravel and vegetated areas, which can be appreciated also because of low flow conditions, emphasizing the composite dynamics typical of a gravel-bed river. These results could improve riverine management considering vegetation structure and dimension, as well as the geomorphic settings of gravel-bed rivers in view of future low flow conditions.

Plastome evolution and phylogenomics of Trichosporeae (Gesneriaceae) with its morphological characters appraisal.

Trichosporeae is the largest and most taxonomically difficult tribe of Gesneriaceae due to its diverse morphology. Previous studies have not clarified the phylogenetic relationships within this tribe on several DNA markers, including the generic relationships within subtribes. Recently, plastid phylogenomics have been successfully employed to resolve the phylogenetic relationships at different taxonomic levels. In this study, plastid phylogenomics were used to explore the relationships within Trichosporeae. Eleven plastomes of Hemiboea were newly reported. Comparative analyses, phylogeny and morphological character evolution within Trichosporeae were conducted on 79 species representing seven subtribes. The Hemiboea plastomes range from 152,742 bp to 153,695 bp in length. Within Trichosporeae, the sampled plastomes range from 152,196 bp to 156,614 bp and GC content from 37.2% to 37.8%. A total of 121-133 genes were annotated in each species, including 80-91 protein-coding genes, 34-37 tRNA genes, and 8 rRNA genes. The contraction and expansion of IR borders were not detected, and gene rearrangements and inversions did not occur. The 13 hypervariable regions were proposed as the potential molecular markers for species identification. A total of 24,299 SNPs and 3,378 indels were inferred, and most of the SNPs were functionally missense and silent variations. There were 1968 SSRs, 2055 tandem repeats and 2802 dispersed repeats. The RSCU and ENC values indicated that the codon usage pattern was conserved in Trichosporeae. Both the phylogenetic frameworks based on the whole plastome and 80 CDSs were basically concordant. The sister relationships between Loxocarpinae and Didymocarpinae were confirmed, and Oreocharis was a sister group of Hemiboea with high support. The morphological characters showed a complex evolutionary pattern of Trichosporeae. Our findings may contribute to future research on genetic diversity, morphological evolutionary patterns, and conservation of the tribe Trichosporeae.

A comprehensive genomic analysis provides insights on the high environmental adaptability of Acinetobacter strains.

Acinetobacter is ubiquitous, and it has a high species diversity and a complex evolutionary pattern. To elucidate the mechanism of its high ability to adapt to various environment, 312 genomes of Acinetobacter strains were analyzed using the phylogenomic and comparative genomics methods. It was revealed that the Acinetobacter genus has an open pan-genome and strong genome plasticity. The pan-genome consists of 47,500 genes, with 818 shared by all the genomes of Acinetobacter, while 22,291 are unique genes. Although Acinetobacter strains do not have a complete glycolytic pathway to directly utilize glucose as carbon source, most of them harbored the n-alkane-degrading genes alkB/alkM (97.1% of tested strains) and almA (96.7% of tested strains), which were responsible for medium-and long-chain n-alkane terminal oxidation reaction, respectively. Most Acinetobacter strains also have catA (93.3% of tested strains) and benAB (92.0% of tested strains) genes that can degrade the aromatic compounds catechol and benzoic acid, respectively. These abilities enable the Acinetobacter strains to easily obtain carbon and energy sources from their environment for survival. The Acinetobacter strains can manage osmotic pressure by accumulating potassium and compatible solutes, including betaine, mannitol, trehalose, glutamic acid, and proline. They respond to oxidative stress by synthesizing superoxide dismutase, catalase, disulfide isomerase, and methionine sulfoxide reductase that repair the damage caused by reactive oxygen species. In addition, most Acinetobacter strains contain many efflux pump genes and resistance genes to manage antibiotic stress and can synthesize a variety of secondary metabolites, including arylpolyene, β-lactone and siderophores among others, to adapt to their environment. These genes enable Acinetobacter strains to survive extreme stresses. The genome of each Acinetobacter strain contained different numbers of prophages (0-12) and genomic islands (GIs) (6-70), and genes related to antibiotic resistance were found in the GIs. The phylogenetic analysis revealed that the alkM and almA genes have a similar evolutionary position with the core genome, indicating that they may have been acquired by vertical gene transfer from their ancestor, while catA, benA, benB and the antibiotic resistance genes could have been acquired by horizontal gene transfer from the other organisms.

A Structured Literature Review Investigating the Current Treatment Landscape in Patients with Richter's Transformation (2011-2021)

Background Richter's transformation (RT) is an uncommon clinicopathological condition that arises as a complication in 5-16% of chronic lymphocytic leukemia (CLL) patients, with an annual incident rate of 0.5-1%. Around 90% of cases present as diffuse large B-cell lymphoma (RT-DLBCL), with Hodgkin Lymphoma variant RT (HL-RT) accounting for 5-10% of transformations. RT is difficult to treat due to its complex molecular and evolutionary patterns. Aims and objectives This literature review aimed to summarize the current guideline recommendations, and identify real-world treatment patterns for patients with RT. Methods Embase, MEDLINE and MEDLINE in-process databases were searched to identify relevant studies. English language, observational treatment pattern studies and treatment guidelines were included (January 2011-December 2021, inclusive). Recent conference proceedings were manually searched (2019-2021, inclusive). Prespecified PICOS criteria were used for study selection. First screening (titles/abstracts), second screening (full text) and extractions were validated by an independent reviewer. Results Of 771 records retrieved, 26 studies (guidelines: n=3; real-world studies: n=23) met the inclusion criteria. Treatment guidelines for patients with RT were identified from NCCN, the British Society of Haematology (BSH) and ESMO (Table 1). Clinical trial enrolment is recommended in patients with DLBCL-RT (NCCN, ESMO, BSH) or HL-RT (NCCN, BSH) at any stage. NCCN and ESMO recommend for clonally unrelated DLBCL-RT to be treated as de novo DLBCL. In clonally related/unknown clonal status DLBCL-RT, NCCN recommend rituximab-based chemoimmunotherapy in 1L, then allogenic Stem Cell Transplant (allo-SCT) in chemo-sensitive patients; and radiation, or pembrolizumab/nivolumab ± ibrutinib in chemo-refractory. ESMO recommend allo-SCT or autogenic-SCT (auto-SCT) for patients with clonally related DLBCL-RT. BSH recommend R-CHOP in treatment naïve DLBCL-RT; and in relapsed refractory (r/r) patients, chemotherapy followed by allo-SCT, CAR-T (in patients after ≥2 prior treatments) or palliative treatment (in heavily pre-treated patients, developing DLBCL-RT on targeted therapy). In HL-RT, NCCN and BSH recommend treatment as per current HL guidelines (i.e., ABVD in 1L). ESMO also recommend conventional chemotherapy in patients with HL-RT. In r/r HL-RT NCCN recommend radiotherapy, auto-SCT, PD-1 inhibitors or chemotherapy. Nine real-world studies provided data on 1L treatment for patients with RT. The most common 1L treatment in DLBCL-RT was chemoimmunotherapy (66-87%) and in HL-RT it was ABVD (59-67%). Other 1L treatments were chemotherapy combinations, targeted therapies (ibrutinib, venetoclax, everolimus), immunotherapies (pembrolizumab) and SCT. The most common systemic treatments in the US were R-CHOP (50-70%) and REPOCH (3.4-28.6%); compared to R-CHOP (19-73%), ABVD (59.1-70%), allo-SCT (3.6-53.9%) and auto-SCT (8.9-58%) in Europe. Treatment pattern data in r/r patients were limited. One US study reported 42% of r/r DLBCL-RT patients received radiotherapy post chemoimmunotherapy. In r/r HL-RT patients who failed to achieve CR with ABVD (n=3) in Italy, subsequent treatments were chemotherapy+allo-SCT, chemoimmunotherapy+auto-SCT or bendamustine-rituximab (33.3% each). Among RT patients treated with BTK inhibitors in the US (n=9), all patients subsequently received chemoimmunotherapy. Studies reporting survival data (Table 2) and response data were largely heterogeneous in terms of study design; outcomes should be interpreted with caution due to small patient numbers. Conclusion Rituximab-based treatments were found to be a mainstay of treatment according to the guidelines. Validating whether real-world treatment patterns were aligned to guidelines was challenging due to limitations in the studies identified (different outcomes, small sample sizes and heterogeneous populations). Patients with r/r RT were underrepresented in the treatment pattern studies. This review highlights the need for novel treatments to improve survival and response outcomes in patients with RT, particularly in patients with r/r disease where current options are limited. All treatment guidelines recommended patient enrolment into clinical trials and increasing enrolment will serve to improve treatment options in this difficult to treat patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Multi-Omics Profiling of Longitudinal Samples Reveals Early Genomic Changes in Follicular Lymphoma

Introduction: Follicular lymphoma (FL) is an indolent malignancy, characterized by multiple relapses during the disease course. Annually around 2-3% of patients experience transformation to aggressive disease (tFL), most commonly to diffuse large B-cell lymphoma (DLBCL). Transformation and progression of disease within 2 years (POD24) are associated with poor prognosis, yet the molecular events underlying these processes are not well understood. The existence of common progenitor cells (CPCs) has been inferred from genetic analyses of longitudinal biopsies. Improved characterization of genetic alterations associated with CPCs in cases with transformation and POD24 may improve our understanding of disease progression, and reveal molecular markers for high-risk disease. Methods: To identify early genetic events during FL pathogenesis and molecular events underlying progression and transformation, we performed whole-exome sequencing of 97 serial tumor biopsies and matched normal samples purified from peripheral blood from 44 FL patients; 22 who experienced transformation (tFL) and 22 with progression of FL (nFL). Nineteen patients(both groups) experienced POD24. SNP6.0 data was available for 93 sequenced tumors and was used to infer allele-specific copy number alterations. Bulk RNA sequencing data was available for 64 sequenced tumors. Several computational tools were applied to identify potential cancer driver genes (IntOGen, MutSig2CV, 2020plus), mutational signatures, and to study clonal evolution (PyClone, ClonEvol). CIBERSORTx was used to infer B-cell specific transcriptomes from bulk RNAseq data. Results: Deep whole exome sequencing confirmed recurrent mutations in epigenetic regulators (CREBBP, KMT2D, EZH2, and EP300) and known copy number alterations. The mutational landscape was similar in nFL and tFL patients, except for higher recurrence of EZH2 mutations in tFL. We used CIBERSORTx to impute B-cell transcriptomes from bulk RNA-sequencing data to identify differentially expressed genes associated with common mutations. We discovered that numerous histone genes were downregulated in biopsies with EZH2 mutations, and in pretreatment samples from tFL patients, potentially contributing to epigenetic deregulation. Based on the mutational pattern in each biopsy, we calculated the genomic distances between longitudinal samples. This revealed great variability in nFL and tFL patients, compatible with complex evolutionary patterns independent of transformation. Tumor clonal evolution analysis identified CREBBP and KMT2D mutations as early genetic events in FL pathogenesis, likely occurring prior to the early CNAs that remained stable throughout disease progression such as gain in 12p and 18p and loss in 6p. Conclusions: Identification of such early and potentially essential genetic events may therefore provide opportunities for early disease detection and monitoring of progression.

Genome-wide analysis of NBS-LRR genes in Rosaceae species reveals distinct evolutionary patterns.

The nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes, one of the largest gene families in plants, are evolving rapidly and playing a critical role in plant resistance to pathogens. In this study, a genome-wide search in 12 Rosaceae genomes screened out 2188 NBS-LRR genes, with the gene number varied distinctively across different species. The reconciled phylogeny revealed 102 ancestral genes (7 RNLs, 26 TNLs, and 69 CNLs), which underwent independent gene duplication and loss events during the divergence of the Rosaceae. The NBS-LRR genes exhibited dynamic and distinct evolutionary patterns in the 12 Rosaceae species due to independent gene duplication/loss events, which resulted the discrepancy of NBS-LRR gene number among Rosaceae species. Specifically, Rubus occidentalis, Potentilla micrantha, Fragaria iinumae and Gillenia trifoliata, displayed a "first expansion and then contraction" evolutionary pattern; Rosa chinensis exhibited a "continuous expansion" pattern; F. vesca had a "expansion followed by contraction, then a further expansion" pattern, three Prunus species and three Maleae species shared a "early sharp expanding to abrupt shrinking" pattern. Overall, this study elucidated the dynamic and complex evolutionary patterns of NBS-LRR genes in the 12 Rosaceae species, and could assist further investigation of mechanisms driving these evolutionary patterns.

Advances in characterization of probiotics and challenges in industrial application

ABSTRACT An unbalanced diet and poor lifestyle are common reasons for numerous health complications in humans. Probiotics are known to provide substantial benefits to human health by producing several bioactive compounds, vitamins, short-chain fatty acids and short peptides. Diets that contain probiotics are limited to curd, yoghurt, kefir, kimchi, etc. However, exploring the identification of more potential probiotics and enhancing their commercial application to improve the nutritional quality would be a significant step to utilizing the maximum benefits. The complex evolution patterns among the probiotics are the hurdles in their characterization and adequate application in the industries and dairy products. This article has mainly discussed the molecular methods of characterization that are based on the analysis of ribosomal RNA, whole genome, and protein markers and profiles. It also has critically emphasized the emerging challenges in industrial applications of probiotics.