The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible.

The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a "mix and match" model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.

Unique gap-related SERS behaviors ofp-aminothiophenol molecules absorbed on TiO2surface in periodic TiO2/Ni nanopillar arrays.

We observed a unique interpillar gap-related surface-enhanced Raman scattering (SERS) behavior ofp-aminothiophenol (PATP) molecules from periodic TiO2nanopillar arrays with three gap sizes of 191, 297 and 401 nm, which is completely different from that on Ag and Ni nanopillar arrays. Especially, the gap-size-dependent charge-transfer (CT) resonance enhancement from TiO2/Ni has been indicated through comparisons of variation trend of SERS intensities with inter-pillar gap size between TiO2/Ni and Ag/TiO2/Ni as well as Ni nanoarrays, and been confirmed by spectra of ultraviolet-visible absorption and photoluminescence. Results demonstrate that the CT resonance enhancement is more susceptible to the change of the gap size compared with the surface plasmon resonance (SPR) enhancement in TiO2/Ni nanoarrays. Hence, SPR and CT enhancement showing different variation trend and rate with the gap size that leads to a different relative contribution of CT resonance to the overall SERS enhancement as gap size changes, and consequently results in a unique gap-related SERS behavior for TiO2/Ni nanoarrays. The present study is not only helpful for investigating SERS mechanism for semiconductors but also providing a method to design and optimize periodic metal/semiconductor SERS substrates in a controllable way.

An injectable, activated neutrophil-derived exosome mimetics/extracellular matrix hybrid hydrogel with antibacterial activity and wound healing promotion effect for diabetic wound therapy.

Chronic diabetic wounds are primarily caused by infection, inflammation, and angiogenesis-related disorders. An ideal approach for treating chronic diabetic wounds is by combining anti-infection strategies, immune microenvironment regulation, and angiogenesis promotion. Vascular endothelial growth factor (VEGF) can promote the proliferation and migration of vascular endothelial cells, thereby promoting angiogenesis. However, the low stability and inability to target lesions limit its application. Polymorphonuclear neutrophil-derived exosomes (PMNExo) exhibit good delivery properties and can be used for the therapeutic delivery of VEGF. Furthermore, they retain the antibacterial ability of polymorphonuclear neutrophils (PMNs). Nonetheless, low PMNExo generation impedes its therapeutic applications. In this study, we prepared exosome mimetics (EM) from PMNs using the extrusion process; as a result, exosome yield significantly improved. To increase the residence of exosomes, an extracellular matrix (ECM) hydrogel, a thermosensitive material that can function as an in situ gel in vivo, was used as an exosome carrier. The active peptides in the ECM regulated the immune microenvironment of the wound. In summary, we loaded ECM with VEGF-encapsulated activated neutrophil exosome mimetics (aPMNEM) to develop VEGF-aPMNEM-ECM hybrid hydrogel for treating chronic wounds. The hydrogel accelerates the regeneration of chronic diabetic wounds. Our study provides a prospective therapy platform involving cytokines for treating different diseases.

Genome-Wide Analysis of bHLH Family Genes and Identification of Members Associated with Cold/Drought-Induced Photoinhibition in Kandelia obovata.

Plant basic helix-loop-helix (bHLH) transcription factors play pivotal roles in responding to stress, including cold and drought. However, it remains unclear how bHLH family genes respond to these stresses in Kandelia obovata. In this study, we identified 75 bHLH members in K. obovata, classified into 11 subfamilies and unevenly distributed across its 18 chromosomes. Collineation analysis revealed that segmental duplication primarily drove the expansion of KobHLH genes. The KobHLH promoters were enriched with elements associated with light response. Through RNA-seq, we identified several cold/drought-associated KobHLH genes. This correlated with decreased net photosynthetic rates (Pn) in the leaves of cold/drought-treated plants. Weighted gene co-expression network analysis (WGCNA) confirmed that 11 KobHLH genes were closely linked to photoinhibition in photosystem II (PS II). Among them, four Phytochrome Interacting Factors (PIFs) involved in chlorophyll metabolism were significantly down-regulated. Subcellular localization showed that KobHLH52 and KobHLH30 were located in the nucleus. Overall, we have comprehensively analyzed the KobHLH family and identified several members associated with photoinhibition under cold or drought stress, which may be helpfulfor further cold/drought-tolerance enhancement and molecular breeding through genetic engineering in K. obovata.

The avocado genome informs deep angiosperm phylogeny, highlights introgressive hybridization, and reveals pathogen-influenced gene space adaptation.

The avocado, Persea americana, is a fruit crop of immense importance to Mexican agriculture with an increasing demand worldwide. Avocado lies in the anciently diverged magnoliid clade of angiosperms, which has a controversial phylogenetic position relative to eudicots and monocots. We sequenced the nuclear genomes of the Mexican avocado race, P. americana var. drymifolia, and the most commercially popular hybrid cultivar, Hass, and anchored the latter to chromosomes using a genetic map. Resequencing of Guatemalan and West Indian varieties revealed that ∼39% of the Hass genome represents Guatemalan source regions introgressed into a Mexican race background. Some introgressed blocks are extremely large, consistent with the recent origin of the cultivar. The avocado lineage experienced 2 lineage-specific polyploidy events during its evolutionary history. Although gene-tree/species-tree phylogenomic results are inconclusive, syntenic ortholog distances to other species place avocado as sister to the enormous monocot and eudicot lineages combined. Duplicate genes descending from polyploidy augmented the transcription factor diversity of avocado, while tandem duplicates enhanced the secondary metabolism of the species. Phenylpropanoid biosynthesis, known to be elicited by Colletotrichum (anthracnose) pathogen infection in avocado, is one enriched function among tandems. Furthermore, transcriptome data show that tandem duplicates are significantly up- and down-regulated in response to anthracnose infection, whereas polyploid duplicates are not, supporting the general view that collections of tandem duplicates contribute evolutionarily recent "tuning knobs" in the genome adaptive landscapes of given species.

Quantitative Trait Locus Mapping of Marsh Spot Disease Resistance in Cranberry Common Bean (Phaseolus vulgaris L.).

Common bean (Phaseolus vulgaris L.) is a food crop that is an important source of dietary proteins and carbohydrates. Marsh spot is a physiological disorder that diminishes seed quality in beans. Prior research suggested that this disease is likely caused by manganese (Mn) deficiency during seed development and that marsh spot resistance is controlled by at least four genes. In this study, genetic mapping was performed to identify quantitative trait loci (QTL) and the potential candidate genes associated with marsh spot resistance. All 138 recombinant inbred lines (RILs) from a bi-parental population were evaluated for marsh spot resistance during five years from 2015 to 2019 in sandy and heavy clay soils in Morden, Manitoba, Canada. The RILs were sequenced using a genotyping by sequencing approach. A total of 52,676 single nucleotide polymorphisms (SNPs) were identified and filtered to generate a high-quality set of 2066 SNPs for QTL mapping. A genetic map based on 1273 SNP markers distributed on 11 chromosomes and covering 1599 cm was constructed. A total of 12 stable and 4 environment-specific QTL were identified using additive effect models, and an additional two epistatic QTL interacting with two of the 16 QTL were identified using an epistasis model. Genome-wide scans of the candidate genes identified 13 metal transport-related candidate genes co-locating within six QTL regions. In particular, two QTL (QTL.3.1 and QTL.3.2) with the highest R2 values (21.8% and 24.5%, respectively) harbored several metal transport genes Phvul.003G086300, Phvul.003G092500, Phvul.003G104900, Phvul.003G099700, and Phvul.003G108900 in a large genomic region of 16.8-27.5 Mb on chromosome 3. These results advance the current understanding of the genetic mechanisms of marsh spot resistance in cranberry common bean and provide new genomic resources for use in genomics-assisted breeding and for candidate gene isolation and functional characterization.

Insights into the Genetic Architecture and Genomic Prediction of Powdery Mildew Resistance in Flax (Linum usitatissimum L.).

Powdery mildew (PM), caused by the fungus Oidium lini in flax, can cause defoliation and reduce seed yield and quality. To date, one major dominant gene (Pm1) and three quantitative trait loci (QTL) on chromosomes 1, 7 and 9 have been reported for PM resistance. To fully dissect the genetic architecture of PM resistance and identify QTL, a diverse flax core collection of 372 accessions augmented with an additional 75 breeding lines were sequenced, and PM resistance was evaluated in the field for eight years (2010-2017) in Morden, Manitoba, Canada. Genome-wide association studies (GWAS) were performed using two single-locus and seven multi-locus statistical models with 247,160 single nucleotide polymorphisms (SNPs) and the phenotypes of the 447 individuals for each year separately as well as the means over years. A total of 349 quantitative trait nucleotides (QTNs) were identified, of which 44 large-effect QTNs (R2 = 10-30%) were highly stable over years. The total number of favourable alleles per accession was significantly correlated with PM resistance (r = 0.74), and genomic selection (GS) models using all identified QTNs generated significantly higher predictive ability (r = 0.93) than those constructed using the 247,160 genome-wide random SNP (r = 0.69), validating the overall reliability of the QTNs and showing the additivity of PM resistance in flax. The QTNs were clustered on the distal ends of all 15 chromosomes, especially on chromosome 5 (0.4-5.6 Mb and 9.4-16.9 Mb) and 13 (4.7-5.2 Mb). To identify candidate genes, a dataset of 3230 SNPs located in resistance gene analogues (RGAs) was used as input for GWAS, from which an additional 39 RGA-specific QTNs were identified. Overall, 269 QTN loci harboured 445 RGAs within the 200 Kb regions spanning the QTNs, including 45 QTNs located within the RGAs. These RGAs supported by significant QTN/SNP allele effects were mostly nucleotide binding site and leucine-rich repeat receptors (NLRs) belonging to either coiled-coil (CC) NLR (CNL) or toll interleukin-1 (TIR) NLR (TNL), receptor-like kinase (RLK), receptor-like protein kinase (RLP), transmembrane-coiled-coil (TM-CC), WRKY, and mildew locus O (MLO) genes. These results constitute an important genomic tool for resistance breeding and gene cloning for PM in flax.

An efficient nanopatterning strategy for controllably fabricating ultra-small gaps as a highly sensitive surface-enhanced Raman scattering platform.

The realization of large-scale and high-density gaps with sizes as small as possible is crucial for designing ultra-sensitive surface-enhanced Raman scattering (SERS) substrates. As known, the ultrathin alumina mask (UTAM) surface nanopatterning technique allows the fabrication of periodic nanoparticle (NP) arrays with 5 nm gaps among the NPs, however, it still faces a significant challenge in realizing the reliable distribution of nanogaps over a large area, because of the unavoidable collapse of the UTAM pore wall during the traditional one-step homothermal pore-widening process. Herein, an efficient two-step poikilothermal pore-widening process was developed to precisely control the pore wall etching of a UTAM, enabling effectively avoiding the fragmentation of the UTAM and finally obtaining a large-scale UTAM with a pore wall thickness of about 5 nm. As a result, large-scale NP arrays with high-density sub-5 nm and even smaller gaps between the neighboring NPs have been realized through applying the as-prepared UTAM as the nanopatterning template. These NP arrays with sub-5 nm gaps show ultrahigh SERS sensitivity (signal enhancement improved by an order of magnitude compared with NP arrays with 5 nm gaps) and good reproducibility, which demonstrates the practical feasibility of this promising two-step pore-widening UTAM technique for the fabrication of high-performance active SERS substrates with large-scale ultra-small nanogaps.

Long-read sequencing uncovers the adaptive topography of a carnivorous plant genome.

Utricularia gibba, the humped bladderwort, is a carnivorous plant that retains a tiny nuclear genome despite at least two rounds of whole genome duplication (WGD) since common ancestry with grapevine and other species. We used a third-generation genome assembly with several complete chromosomes to reconstruct the two most recent lineage-specific ancestral genomes that led to the modern U. gibba genome structure. Patterns of subgenome dominance in the most recent WGD, both architectural and transcriptional, are suggestive of allopolyploidization, which may have generated genomic novelty and led to instantaneous speciation. Syntenic duplicates retained in polyploid blocks are enriched for transcription factor functions, whereas gene copies derived from ongoing tandem duplication events are enriched in metabolic functions potentially important for a carnivorous plant. Among these are tandem arrays of cysteine protease genes with trap-specific expression that evolved within a protein family known to be useful in the digestion of animal prey. Further enriched functions among tandem duplicates (also with trap-enhanced expression) include peptide transport (intercellular movement of broken-down prey proteins), ATPase activities (bladder-trap acidification and transmembrane nutrient transport), hydrolase and chitinase activities (breakdown of prey polysaccharides), and cell-wall dynamic components possibly associated with active bladder movements. Whereas independently polyploid Arabidopsis syntenic gene duplicates are similarly enriched for transcriptional regulatory activities, Arabidopsis tandems are distinct from those of U. gibba, while still metabolic and likely reflecting unique adaptations of that species. Taken together, these findings highlight the special importance of tandem duplications in the adaptive landscapes of a carnivorous plant genome.

Genomic Prediction Accuracy of Seven Breeding Selection Traits Improved by QTL Identification in Flax.

Molecular markers are one of the major factors affecting genomic prediction accuracy and the cost of genomic selection (GS). Previous studies have indicated that the use of quantitative trait loci (QTL) as markers in GS significantly increases prediction accuracy compared with genome-wide random single nucleotide polymorphism (SNP) markers. To optimize the selection of QTL markers in GS, a set of 260 lines from bi-parental populations with 17,277 genome-wide SNPs were used to evaluate the prediction accuracy for seed yield (YLD), days to maturity (DTM), iodine value (IOD), protein (PRO), oil (OIL), linoleic acid (LIO), and linolenic acid (LIN) contents. These seven traits were phenotyped over four years at two locations. Identification of quantitative trait nucleotides (QTNs) for the seven traits was performed using three types of statistical models for genome-wide association study: two SNP-based single-locus (SS), seven SNP-based multi-locus (SM), and one haplotype-block-based multi-locus (BM) models. The identified QTNs were then grouped into QTL based on haplotype blocks. For all seven traits, 133, 355, and 1,208 unique QTL were identified by SS, SM, and BM, respectively. A total of 1420 unique QTL were obtained by SS+SM+BM, ranging from 254 (OIL, LIO) to 361 (YLD) for individual traits, whereas a total of 427 unique QTL were achieved by SS+SM, ranging from 56 (YLD) to 128 (LIO). SS models alone did not identify sufficient QTL for GS. The highest prediction accuracies were obtained using single-trait QTL identified by SS+SM+BM for OIL (0.929 ± 0.016), PRO (0.893 ± 0.023), YLD (0.892 ± 0.030), and DTM (0.730 ± 0.062), and by SS+SM for LIN (0.837 ± 0.053), LIO (0.835 ± 0.049), and IOD (0.835 ± 0.041). In terms of the number of QTL markers and prediction accuracy, SS+SM outperformed other models or combinations thereof. The use of all SNPs or QTL of all seven traits significantly reduced the prediction accuracy of traits. The results further validated that QTL outperformed high-density genome-wide random markers, and demonstrated that the combined use of single and multi-locus models can effectively identify a comprehensive set of QTL that improve prediction accuracy, but further studies on detection and removal of redundant or false-positive QTL to maximize prediction accuracy and minimize the number of QTL markers in GS are warranted.

Distinguishing successive ancient polyploidy levels based on genome-internal syntenic alignment.

BACKGROUND: A basic tool for studying the polyploidization history of a genome, especially in plants, is the distribution of duplicate gene similarities in syntenically aligned regions of a genome. This distribution can usually be decomposed into two or more components identifiable by peaks, or local maxima, each representing a different polyploidization event. The distributions may be generated by means of a discrete time branching process, followed by a sequence divergence model. The branching process, as well as the inference of fractionation rates based on it, requires knowledge of the ploidy level of each event, which cannot be directly inferred from the pair similarity distribution. RESULTS: For a sequence of two events of unknown ploidy, either tetraploid, giving rise to whole genome doubling (WGD), or hexaploid, giving rise to whole genome tripling (WGT), we base our analysis on triples of similar genes. We calculate the probability of the four triplet types with origins in one or the other event, or both, and impose a mutational model so that the distribution resembles the original data. Using a ML transition point in the similarities between the two events as a discriminator for the hypothesized origin of each similarity, we calculate the predicted number of triplets of each type for each model combining WGT and/or WGD. This yields a predicted profile of triplet types for each model. We compare the observed and predicted triplet profiles for each model to confirm the polyploidization history of durian, poplar and cabbage. CONCLUSIONS: We have developed a way of inferring the ploidy of up to three successive WGD and/or WGT events by estimating the time of origin of each of the similarities in triples of genes. This may be generalized to a larger number of events and to higher ploidies.

Pinning down ploidy in paleopolyploid plants.

BACKGROUND: Fractionation is the genome-wide process of losing one gene per duplicate pair following whole genome multiplication (doubling, tripling, …). This is important in the evolution of plants over tens of millions of years, because of their repeated cycles of genome multiplication and fractionation. One type of evidence in the study of these processes is the frequency distribution of similarities between the two genes, over all the duplicate pairs in the genome. RESULTS: We study modeling and inference problems around the processes of fractionation and whole genome multiplication focusing first on the frequency distribution of similarities of duplicate pairs in the genome. Our birth-and-death model accounts for repeated duplication, triplication or other multiplication events, as well as fractionation rates among multiple progeny of a single gene specific to each event. It also has a biologically and combinatorially well-motivated way of handling the tendency for at least one sibling to survive fractionation. The method settles previously unexplored questions about the expected number of gene pairs tracing their ancestry back to each multiplication event. We exemplify the algebraic concepts inherent in our models and on Brassica rapa, whose evolutionary history is well-known. We demonstrate the quantitative analysis of high-similarity gene pairs and triples to confirm the known ploidies of events in the lineage of B. rapa. CONCLUSIONS: Our birth-and-death model accounts for the similarity distribution of paralogs in terms of multiple rounds of whole genome multiplication and fractionation. An analysis of high-similarity gene triples confirms the recent Brassica triplication.

Resolution effects in reconstructing ancestral genomes.

BACKGROUND: The reconstruction of ancestral genomes must deal with the problem of resolution, necessarily involving a trade-off between trying to identify genomic details and being overwhelmed by noise at higher resolutions. RESULTS: We use the median reconstruction at the synteny block level, of the ancestral genome of the order Gentianales, based on coffee, Rhazya stricta and grape, to exemplify the effects of resolution (granularity) on comparative genomic analyses. CONCLUSIONS: We show how decreased resolution blurs the differences between evolving genomes, with respect to rate, mutational process and other characteristics.

Genomic Analysis of the ASMT Gene Family in Solanum lycopersicum.

Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the integration of the structural features, phylogenetic relationships, exon/intron configuration, and expression profile during growth and development, as well as biotic stresses. The results revealed that the tomato genome encoded a minimum of 14 members, containing three probable encoded pseudogenes. Chromosome mapping indicated that the family had probably expanded via tandem duplication events. Genome-wide RNA-seq and qRT-PCR based gene expression analysis revealed that almost half of the SlASMT genes were expressed in at least one of the experimental stages studied and also showed differential accumulation. Furthermore, the tandem duplicated SlASMT genes showed differential expression levels, which indicated probable functional divergence during the course of the evolution. Finally, this study also determined that some SlASMT genes were induced by multiple pathogens. The results suggested that these genes could be involved in tomato plant response to biotic stresses.

Locating rearrangement events in a phylogeny based on highly fragmented assemblies.

BACKGROUND: The inference of genome rearrangement operations requires complete genome assemblies as input data, since a rearrangement can involve an arbitrarily large proportion of one or more chromosomes. Most genome sequence projects, especially those on non-model organisms for which no physical map exists, produce very fragmented assembles, so that a rearranged fragment may be impossible to identify because its two endpoints are on different scaffolds. However, breakpoints are easily identified, as long as they do not coincide with scaffold ends. For the phylogenetic context, in comparing a fragmented assembly with a number of complete assemblies, certain combinatorial constraints on breakpoints can be derived. We ask to what extent we can use breakpoint data between a fragmented genome and a number of complete genomes to recover all the arrangements in a phylogeny. RESULTS: We simulate genomic evolution via chromosomal inversion, fragmenting one of the genomes into a large number of scaffolds to represent the incompleteness of assembly. We identify all the breakpoints between this genome and the remainder. We devise an algorithm which takes these breakpoints into account in trying to determine on which branch of the phylogeny a rearrangement event occurred. We present an analysis of the dependence of recovery rates on scaffold size and rearrangement rate, and show that the true tree, the one on which the rearrangement simulation was performed, tends to be most parsimonious in estimating the number of true events inferred. CONCLUSIONS: It is somewhat surprising that the breakpoints identified just between the fragmented genome and each of the others suffice to recover most of the rearrangements produced by the simulations. This holds even in parts of the phylogeny disjoint from the lineage of the fragmented genome.

Structural vs. functional mechanisms of duplicate gene loss following whole genome doubling.

BACKGROUND: The loss of duplicate genes - fractionation - after whole genome doubling (WGD) is the subject to a debate as to whether it proceeds gene by gene or through deletion of multi-gene chromosomal segments. RESULTS: WGD produces two copies of every chromosome, namely two identical copies of a sequence of genes. We assume deletion events excise a geometrically distributed number of consecutive genes with mean µ ≥ 1, and these events can combine to produce single-copy runs of length l. If µ = 1, the process is gene-by-gene. If µ > 1, the process at least occasionally excises more than one gene at a time. In the latter case if deletions overlap, the later one simply extends the existing run of single-copy genes. We explore aspects of the predicted distribution of the lengths of single-copy regions analytically, but resort to simulations to show how observing run lengths l allows us to discriminate between the two hypotheses. CONCLUSIONS: Deletion run length distributions can discriminate between gene-by-gene fractionation and deletion of segments of geometrically distributed length, even if µ is only slightly larger than 1, as long as the genome is large enough and fractionation has not proceeded too far towards completion.

Syntenic block overlap multiplicities with a panel of reference genomes provide a signature of ancient polyploidization events.

BACKGROUND: Following whole genome duplication (WGD), there is a compact distribution of gene similarities within the genome reflecting duplicate pairs of all the genes in the genome. With time, the distribution broadens and loses volume due to variable decay of duplicate gene similarity and to the process of duplicate gene loss. If there are two WGD, the older one becomes so reduced and broad that it merges with the tail of the distributions resulting from more recent events, and it becomes difficult to distinguish them. The goal of this paper is to advance statistical methods of identifying, or at least counting, the WGD events in the lineage of a given genome. METHODS: For a set of 15 angiosperm genomes, we analyze all 15 × 14 = 210 ordered pairs of target genome versus reference genome, using SynMap to find syntenic blocks. We consider all sets of B ≥ 2 syntenic blocks in the target genome that overlap in the reference genome as evidence of WGD activity in the target, whether it be one event or several. We hypothesize that in fitting an exponential function to the tail of the empirical distribution f (B) of block multiplicities, the size of the exponent will reflect the amount of WGD in the history of the target genome. RESULTS: By amalgamating the results from all reference genomes, a range of values of SynMap parameters, and alternative cutoff points for the tail, we find a clear pattern whereby multiple-WGD core eudicots have the smallest (negative) exponents, followed by core eudicots with only the single "γ" triplication in their history, followed by a non-core eudicot with a single WGD, followed by the monocots, with a basal angiosperm, the WGD-free Amborella having the largest exponent. CONCLUSION: The hypothesis that the exponent of the fit to the tail of the multiplicity distribution is a signature of the amount of WGD is verified, but there is also a clear complicating factor in the monocot clade, where a history of multiple WGD is not reflected in a small exponent.

Near-medians that avoid the corners; a combinatorial probability approach.

BACKGROUND: The breakpoint median for a set of k ≥ 3 random genomes tends to approach (any) one of these genomes ("corners") as genome length increases, although there are diminishing proportion of medians equidistant from all k ("medians in the middle"). Algorithms are likely to miss the latter, and this has consequences for the general case where input genomes share some or many gene adjacencies, where the tendency for the median to be closer to one input genome may be an artifact of the corner tendency. RESULTS: We present a simple sampling procedure for constructing a "near median" that represents a compromise among k random genomes and that has only a slightly greater breakpoint distance to all of them than the median does. We generalize to the realistic case where genomes share varying proportions of gene adjacencies. We present a supplementary sampling scheme that brings the constructed genome even closer to median status. CONCLUSIONS: Our approach is of particular use in the phylogenetic context where medians are repeatedly calculated at ancestral nodes, and where the corner effect prevents different parts of the phylogeny from communicating with each other.

Gene families as soft cliques with backbones: Amborella contrasted with other flowering plants.

BACKGROUND: Chaining is a major problem in constructing gene families. RESULTS: We define a new kind of cluster on graphs with strong and weak edges: soft cliques with backbones (SCWiB). This differs from other definitions in how it controls the "chaining effect", by ensuring clusters satisfy a tolerant edge density criterion that takes into account cluster size. We implement algorithms for decomposing a graph of similarities into SCWiBs. We compare examples of output from SCWiB and the Markov Cluster Algorithm (MCL), and also compare some curated Arabidopsis thaliana gene families with the results of automatic clustering. We apply our method to 44 published angiosperm genomes with annotation, and discover that Amborella trichopoda is distinct from all the others in having substantially and systematically smaller proportions of moderate- and large-size gene families. CONCLUSIONS: We offer several possible evolutionary explanations for this result.

Construction and multicohort validation of a colon cancer prognostic risk score system based on big data of neutrophil-associated differentially expressed genes.

Objective: To investigate the role of neutrophils in colon cancer progression. Methods: Genetic data from 1,273 patients with colon cancer were procured from public databases and categorized based on genes linked to neutrophils through an unsupervised clustering approach. Through univariate Cox regression analysis, differentially expressed genes (DEGs) influencing overall survival (OS) were identified, forming the basis for establishing a prognostic risk score (PRS) system specific to colon cancer. Additionally, the correlation between PRS and patient prognosis, immune cell infiltration, and intratumoral gene mutations were analyzed. Validation of PRS as an indicator for "pan-tumor" immunotherapy was conducted using four distinct immunotherapy cohorts. Results: The research identified two distinct subtypes of colon cancer, namely Cluster A and B, with patients in Cluster B demonstrating remarkably superior prognoses over those in Cluster A. A total of 17 genes affecting OS were screened based on 109 DEGs between the two cluster for constructing the PRS system. Notably, individuals classified under the high-PRS group (PRShigh) exhibited poorer prognoses, significantly linked with immune cell infiltration, an immunosuppressive tumor microenvironment, and increased genomic mutations. Remarkably, analysis of immunotherapy cohorts indicated that patients with PRShigh exhibited enhanced clinical responses, a higher rate of progression-free events, and improved overall survival post-immunotherapy. The PRS system, developed based on tumor typing utilizing neutrophil-associated genes, exhibited a strong correlation with prognostic elements in colon cancer and emerged as a vital predictor of "pan-tumor" immunotherapy efficacy. Conclusions: PRS serves as a prognostic model for patients with colon cancer and holds the potential to act as a "pan-tumor" universal marker for assessing immunotherapy efficacy across different tumor types. The study findings lay a foundation for novel antitumor strategies centered on neutrophil-focused approaches.