Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass.

Long-term climate change and periodic environmental extremes threaten food and fuel security1 and global crop productivity2-4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6-knowledge that has been limited to a small number of well-studied model systems. Here we present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum). Analysis of biomass and survival among 732 resequenced genotypes, which were grown across 10 common gardens that span 1,800 km of latitude, jointly revealed extensive genomic evidence of climate adaptation. Climate-gene-biomass associations were abundant but varied considerably among deeply diverged gene pools. Furthermore, we found that gene flow accelerated climate adaptation during the postglacial colonization of northern habitats through introgression of alleles from a pre-adapted northern gene pool. The polyploid nature of switchgrass also enhanced adaptive potential through the fractionation of gene function, as there was an increased level of heritable genetic diversity on the nondominant subgenome. In addition to investigating patterns of climate adaptation, the genome resources and gene-trait associations developed here provide breeders with the necessary tools to increase switchgrass yield for the sustainable production of bioenergy.

Genomics of the origin and evolution of Citrus.

The genus Citrus, comprising some of the most widely cultivated fruit crops worldwide, includes an uncertain number of species. Here we describe ten natural citrus species, using genomic, phylogenetic and biogeographic analyses of 60 accessions representing diverse citrus germ plasms, and propose that citrus diversified during the late Miocene epoch through a rapid southeast Asian radiation that correlates with a marked weakening of the monsoons. A second radiation enabled by migration across the Wallace line gave rise to the Australian limes in the early Pliocene epoch. Further identification and analyses of hybrids and admixed genomes provides insights into the genealogy of major commercial cultivars of citrus. Among mandarins and sweet orange, we find an extensive network of relatedness that illuminates the domestication of these groups. Widespread pummelo admixture among these mandarins and its correlation with fruit size and acidity suggests a plausible role of pummelo introgression in the selection of palatable mandarins. This work provides a new evolutionary framework for the genus Citrus.

A chromosome-scale reference genome of trifoliate orange (Poncirus trifoliata) provides insights into disease resistance, cold tolerance and genome evolution in Citrus.

Trifoliate orange (Poncirus trifoliata), a deciduous close relative of evergreen Citrus, has important traits for citrus production, including tolerance/resistance to citrus greening disease (Huanglongbing, HLB) and other major diseases, and cold tolerance. It has been one of the most important rootstocks, and one of the most valuable sources of resistance and tolerance genes for citrus. Here we present a high-quality, chromosome-scale genome assembly of P. trifoliata. The 264.9-Mb assembly contains nine chromosomal pseudomolecules with 25 538 protein-coding genes, covering 97.2% of the estimated gene space. Comparative analyses of P. trifoliata and nine Citrus genomes revealed 605 species-specific genes and six rapidly evolving gene families in the P. trifoliata genome. Poncirus trifoliata has evolved specific adaptation in the C-repeat/DREB binding factor (CBF)-dependent and CBF-independent cold signaling pathways to tolerate cold. We identified candidate genes within quantitative trait loci for HLB tolerance, and at the loci for resistance to citrus tristeza virus and citrus nematode. Genetic diversity analysis of Poncirus accessions and Poncirus/Citrus hybrids shows a narrow genetic base in the US germplasm collection, and points to the importance of collecting and preserving more natural genetic variation. Two phenotypically divergent Poncirus accessions are found to be clonally related, supporting a previous conjecture that dwarf Flying Dragon originated as a mutant of a non-dwarfing type. The high-quality genome reveals features and evolutionary insights of Poncirus, and it will serve as a valuable resource for genetic, genomic and molecular research and manipulation in citrus.

Countering Youth's Negative Stereotypes of Teens Fosters Constructive Behavior.

Adolescence can be a time of unconstructive behavior for many youth. This research examined if an intervention countering youth's stereotypes of teens as irresponsible fosters their constructive behavior. In two experimental intervention studies (Ns = 124 and 319) with seventh graders, stereotypes of teens as irresponsible were described as inaccurate portrayals; youth then provided their own observations of teens acting responsibly. Youth in this counterstereotyping intervention (vs. the control) held higher intentions for academic engagement and performed better on an academic task (i.e., a word-search puzzle). Over the 3 days following the intervention, their academic engagement was higher. Youth's risk taking was also reduced. Redirecting youth to see teens as responsible has the potential to provide a foundation for flourishing.

Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children.

BACKGROUND/AIMS: The molecules involved in nephrotic syndrome (NS) have not been fully clarified. Mitochondrial fission proteins are found to be involved in podocyte injury in vitro. Increased glomerular expression of mitochondrial fission proteins was found in adriamycin nephropathy in our previous study. Whether or not mitochondrial fission proteins are involved in podocyte injury in NS is not clear. This study explored the glomerular expression and possible pathological significance of mitochondrial fission-associated proteins, including dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1), in children with NS. METHODS: Eighteen children with primary NS, including 6 with minimal change disease, 6 with focal segmental glomerulosclerosis, 6 with membranous nephropathy, 6 children with isolated haematuria and 3 normal controls were included. The glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1, urinary protein measurements, and podocyte mitochondrial density under electron microscopy were investigated and compared. RESULTS: Glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 was mainly increased in children with NS with membranous nephropathy. No relationship was found between glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 and podocyte mitochondrial density or urinary protein measurements. CONCLUSION: Glomerular overproduction of Drp1, phospho-Drp1 (Ser 616) and Fis1 occurred mainly in children with membranous nephropathy. The pathological significance deserves further investigation.

Long-term treatment by ACE inhibitors and angiotensin receptor blockers in children with Alport syndrome.

BACKGROUND: The aim of this study was to analyze the long-term efficacy and safety of angiotensin-converting enzyme inhibitor (ACEi) and ACEi + angiotensin receptor blocker (ARB) treatments in a cohort of children with Alport syndrome (AS). METHODS: This was a respective review of 79 Chinese children with AS who received ACEi alone or combined ACEi + ARB therapy. RESULTS: The mean age of the pediatric patients with AS at onset of treatment was 8.6 ± 4.1 (range 1.5-16.3) years. The mean duration of follow-up was 2.5 ± 1.8 (range 0.5-7.8) years. For analysis, we separated the children into three groups according to proteinuria level before treatment, namely, <25, 25-50, and ≥50 mg/kg/day, respectively; after 1 year of treatment the proteinuria had decreased from 11.0 to 9.7 mg/kg/day, from 34.6 to 15.2 mg/kg/day, and from 73.0 to 50.0 mg/kg/day in each group, respectively. Proteinuria decreased significantly during the first 2 years of treatment and was stable from the third to fifth years of treatment. There was no statistically significant difference in the antiproteinuric effect of the ACEi and ACEi + ARB treatments in patients with severe or less severe mutations after 1 year of therapy. Five children stopped the ACEi + ARB treatment due to a decline in creatinine clearance. CONCLUSION: Our findings demonstrate that early and long-term ACEi and ARB treatments in children with AS is efficient and well tolerated. The antiproteinuric effect of ACEi and ARB is of equal value in children with severe and less severe mutations in the COL4An gene.

Cultural adaptation in measuring common client characteristics with an urban Mainland Chinese sample.

OBJECTIVES: This study aimed to develop a culturally adapted version of the Systematic Treatment Selection-Innerlife (STS) in China. METHODS: A total of 300 nonclinical participants collected from Mainland China and 240 nonclinical US participants were drawn from archival data. A Chinese version of the STS was developed, using translation and back-translation procedures. After confirmatory factor analysis (CFA) of the original STS sub scales failed on both samples, exploratory factor analysis (EFA) was then used to access whether a simple structure would emerge on these STS treatment items. Parallel analysis and minimum average partial were used to determine the number of factor to retain. RESULTS: Three cross-cultural factors were found in this study, Internalized Distress, Externalized Distress and interpersonal relations. CONCLUSIONS: This supported that regardless of whether one is in presumably different cultural contexts of the USA or China, psychological distress is expressed in a few basic channels of internalized distress, externalized distress, and interpersonal relations, from which different manifestations in different culture were also discussed.

[Effects of different culture conditions on main chemical compositions of Anoectochilus roxburghii].

OBJECTIVE: To investigate the effects of different culture conditions on the main chemical compositions of Anoectochilus roxburghii, so as to determine the optimum culture conditions and provide theoretical support for large-scale production of Anoectochilus roxburghii. METHODS: The light qualities, photoperiods and induction periods were changed to regulate the main chemical compositions of Anoectochilus roxburghii. RESULTS: The contents of total flavonoids, quercetin, isorhamnetin and kaempferol in blue light were higher than that in yellow light, the worst was under red light. There was the highest total flavonoids, kaempferol and isorhamnetin content in photoperiod of 14 h/d. After one month inoculation, the total flavonoids, quercetin, isorhamnetin and kaempferol contents were the highest. CONCLUSION: The results show that the optimum culture condition is: inducted 15 days with blue light inoculated one month later at the photoperiod of 14 h/d.

Fabry disease caused by the GLA p.Gly183Asp (p.G183D) variant: Clinical profile of a serious phenotype.

Background: The detailed clinical phenotype of patients carrying the α-galactosidase gene (GLA) c.548 G > A/p.Gly183Asp (p.G183D) variant in Fabry disease (FD) has not been thoroughly documented in the existing literature. Methods: This paper offers a meticulous overview of the clinical phenotype and relevant auxiliary examination results of nine confirmed FD patients with the p.G183D gene variant from two families. Pedigree analysis was conducted on two male patients with the gene variant, followed by biochemical and genetic screening of all high-risk relatives. Subsequently, evaluation of multiple organ systems and comprehensive instrument assessment were performed on heterozygotes of the p.G183D gene variant. Results: The study revealed that all patients exhibited varying degrees of cardiac involvement, with two demonstrating left ventricular wall thickness exceeding 15 mm on echocardiography, and the remaining six exceeding 11 mm. Impaired renal function was evident in all six patients with available blood test data, two of whom underwent kidney transplantation. Eight cases reported neuropathic pain, and five experienced varying degrees of stroke or transient ischemic attack (TIA). Conclusion: This study indicates that the GLA p.G183D gene variant can induce premature organ damage, particularly affecting the heart, kidneys, and nervous system.

Development and Assessment of SNP Genotyping Arrays for Citrus and Its Close Relatives.

Rapid advancements in technologies provide various tools to analyze fruit crop genomes to better understand genetic diversity and relationships and aid in breeding. Genome-wide single nucleotide polymorphism (SNP) genotyping arrays offer highly multiplexed assays at a relatively low cost per data point. We report the development and validation of 1.4M SNP Axiom® Citrus HD Genotyping Array (Citrus 15AX 1 and Citrus 15AX 2) and 58K SNP Axiom® Citrus Genotyping Arrays for Citrus and close relatives. SNPs represented were chosen from a citrus variant discovery panel consisting of 41 diverse whole-genome re-sequenced accessions of Citrus and close relatives, including eight progenitor citrus species. SNPs chosen mainly target putative genic regions of the genome and are accurately called in both Citrus and its closely related genera while providing good coverage of the nuclear and chloroplast genomes. Reproducibility of the arrays was nearly 100%, with a large majority of the SNPs classified as the most stringent class of markers, "PolyHighResolution" (PHR) polymorphisms. Concordance between SNP calls in sequence data and array data average 98%. Phylogenies generated with array data were similar to those with comparable sequence data and little affected by 3 to 5% genotyping error. Both arrays are publicly available.

Recurrent heart failure hospitalizations in heart failure with preserved ejection fraction: an analysis of TOPCAT trial.

AIMS: Recurrent heart failure hospitalization (HFH) is an important feature of the progression of heart failure (HF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, we analysed risk factors for recurrent HFH events in HF patients with preserved ejection fraction (HFpEF) and developed a risk prediction model for recurrent HFH. METHODS AND RESULTS: This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n = 1767). Recurrent HFH was defined as two or more hospitalizations for HF during the follow-up period. Lasso regression and multivariate logistic regression were used to screen the risk factors, and the risk prediction model of recurrent HFH was established. During a median follow-up period of 3.4 (95% confidence interval: 3.3-3.6) years, 72.2% (542 of 751 total hospitalizations) of HFH events occurred in 9.4% (n = 163) of patients with recurrent HFHs. Patients in the recurrent HFH group had higher cardiovascular mortality rate [6.2 per 100 patient-years (PY) vs. 3.8 per 100 PY, P = 0.016] and all-cause mortality rate (10.0 per 100 PY vs. 6.8 per 100 PY, P = 0.015) than those in the non-recurrent HFH group. The model consisting of nine predictors has moderate predictive power for recurrent HFH events in patients with HFpEF (AUC = 0.75, Brier score = 0.08). Decision curve analysis showed a net clinical benefit from the application of the prediction model. CONCLUSIONS: In patients with HFpEF, the majority of HFHs occur in a small proportion of patients with repeated hospitalizations, who typically have more comorbidities and are at higher risk of death. The predictive model developed in this study helps to identify patients at high risk of recurrent HFH.

Whole-proteome phylogeny of prokaryotes by feature frequency profiles: An alignment-free method with optimal feature resolution.

We present a whole-proteome phylogeny of prokaryotes constructed by comparing feature frequency profiles (FFPs) of whole proteomes. Features are l-mers of amino acids, and each organism is represented by a profile of frequencies of all features. The selection of feature length is critical in the FFP method, and we have developed a procedure for identifying the optimal feature lengths for inferring the phylogeny of prokaryotes, strictly speaking, a proteome phylogeny. Our FFP trees are constructed with whole proteomes of 884 prokaryotes, 16 unicellular eukaryotes, and 2 random sequences. To highlight the branching order of major groups, we present a simplified proteome FFP tree of monophyletic class or phylum with branch support. In our whole-proteome FFP trees (i) Archaea, Bacteria, Eukaryota, and a random sequence outgroup are clearly separated; (ii) Archaea and Bacteria form a sister group when rooted with random sequences; (iii) Planctomycetes, which possesses an intracellular membrane compartment, is placed at the basal position of the Bacteria domain; (iv) almost all groups are monophyletic in prokaryotes at most taxonomic levels, but many differences in the branching order of major groups are observed between our proteome FFP tree and trees built with other methods; and (v) previously "unclassified" genomes may be assigned to the most likely taxa. We describe notable similarities and differences between our FFP trees and those based on other methods in grouping and phylogeny of prokaryotes.

[Guiding values of facial nerve 3D-TOF-MRA and 3D-FIESTA scan for primary hemifacial spasm operation].

OBJECTIVE: To explore the operative guiding values of facial nerve three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and three-dimensional fast imaging employing steady state acquisition three-dimensional fast imaging employing steady state acquisition (3D-FIESTA) scan. METHODS: A total of 125 cases of primary hemifacial spasm was treated at our hospital from 2004 to 2012. Among them, 80 cases received preoperative facial nerve MRA scan. The imaging and intraoperative findings were compared to determine the responsible blood vessels. RESULTS: Responsible blood vessels were found in all 80 cases. Sixty patients (75%) had the involvement of single vessel of anterior inferior cerebellar artery (AICA, n = 57), posterior inferior cerebellar artery (PICA, n = 1), superior cerebellar artery (SCA, n = 1) and vertebral artery (VA, n = 1). Two or more vessels were implicated in 9 patients (11.25%). The culprits were AICA+ internal auditory artery (n = 8) and PICA+ internal auditory artery (n = 1). The source of responsible vessels of 11 cases could not be determined before surgery. Through intraoperative anatomy, 59 patients had single vessel lesions, including AICA (n = 53), PICA (n = 4), SCA (n = 1) and VA (n = 1). Among 14 cases of multiple vessels, there were AICA + internal auditory artery (n = 7), internal auditory artery + PICA (n = 2), AICA + brain stem perforating artery (n = 3) and AICA + vein (n = 2). Seven cases were uncertain. No significant statistical difference existed between two groups. CONCLUSION: Facial nerve 3D-TOF-MRA and 3D-FIESTA scan can identify the status of responsible blood vessels to guide operations.

[Study on a collagenase protocol to extract DNA from remnant feathers in edible bird's nest].

OBJECTIVE: To establish a method for extracting genomic DNA from rudimental bird feather from the precious edible bird's nest (EBN) harvested from the swiftlet cave. METHODS: Observed the EBN using endoscopic and studied the influence of adding collagenase on the extracting yield of DNA. PCR amplification and sequencing for the extraction was also conducted. RESULTS: Collagenase was used in addition to protease K which could substantively increase the DNA yield. The DNA extracted by this method could be used for PCR and other molecular biology analyses. CONCLUSION: This method can be applied to identify the species types in biological products, especially for animal tissue materials that rich in collagen.

Abalone visceral peptides containing Cys and Tyr exhibit strong in vitro antioxidant activity and cytoprotective effects against oxidative damage.

The in vitro antioxidation and cytoprotection of abalone visceral peptides against oxidative damage were investigated. Results show that the DPPH· scavenging activities of the 16 chemically synthesized peptides were significantly and positively correlated with their reducing power. Their scavenging activities against ABTS·+ were positively correlated with their ability to inhibit linoleic acid oxidation. Only Cys containing peptides exhibited good DPPH· scavenging activity, while only Tyr containing peptides showed significant ABTS·+ scavenging activity. In the cytoprotection assay, all four representative peptides significantly increased the viability of H2O2-damaged LO2 cells and the activities of GSH-Px, CAT, and SOD, and all decreased MDA levels and LDH leakage, in which the Cys-containing peptides were more effective at increasing the activities of antioxidant enzymes, while the Tyr-containing peptides were more effective at decreasing MDA levels and LDH leakage. Abalone visceral peptides containing both Cys and Tyr exhibit strong in vitro and cellular antioxidation.

Response surface methodology-optimized extraction of flavonoids from pomelo peels and isolation of naringin with antioxidant activities by Sephadex LH20 gel chromatography.

In this study, flavonoids were extracted from pomelo peels and naringin was isolated from the flavonoid extract. The effects of extraction parameters, namely, ethanol concentration, solid-to-liquid ratio, and extraction time, on the yield of flavonoids extracted from pomelo peels were analyzed according to the Box-Behnken design of response surface methodology. The experimental conditions for flavonoid extraction were optimized, and naringin was separated from the extracted flavonoids using Sephadex LH-20 column chromatography. Experimental results showed that the influence of factors on the extraction rate of flavonoids from pomelo peels was in the order of ethanol concentration > solid-to-liquid ratio > extraction time, and the optimal extraction parameters were 85% ethanol concentration, 1:20 solid-to-liquid ratio, and 4-h extraction time for extracting flavonoids from pomelo peels. Under these conditions, the yield of flavonoids was 6.07 ± 0.06 mg/g. After three times of extraction, the flavonoid extraction rate reached 96.55%, and the residual naringin in the pomelo peels was 0.017 mg/g, at which point the bitterness in the pomelo peels disappeared. Two components, namely, PF1 and PF2, were separated from the crude flavonoid of pomelo peels through Sephadex LH20 column chromatography. PF2 was identified as naringin by high-performance liquid chromatography tandem mass spectrometry, with a purity of 95.7 ± 0.23%. Both flavonoids and PF2 exhibited good in vitro radicals scavenging activities on DPPH, ABTS, superoxide anion and hydroxyl.

Longer time in blood pressure target range improves cardiovascular outcomes among patients with Type 2 diabetes: A secondary analysis of a randomized clinical trial.

AIMS: To examine the prognostic value of time in target range (TIR) with adverse outcomes and validate it with common blood pressure (BP) metrics among patients with Type 2 diabetes mellitus. METHODS: We performed a post hoc analysis of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. TIR for each subject was calculated using linear interpolation and an SBP target range of 110 to 130 mmHg. Cox models were used to assess the association of TIR and other BP metrics with the rate of clinical outcomes. RESULTS: A higher TIR (61.9-100.0 %) was associated with a 46 % reduction in major adverse cardiovascular events (MACE) (hazard ratio [HR]:0.54; 95 % CI: 0.43, 0.67) compared with TIR 0-22.9 %. Results were similar for stroke (0.19; 0.10, 0.36), myocardial infarction (0.67; 0.51, 0.89), heart failure (0.47; 0.33, 0.66), cardiovascular death (0.63; 0.42, 0.93) and all-cause mortality (0.70; 0.54, 0.91). Further analyses suggested a curvilinear association of TIR with MACE, and this association was independent with baseline, final SBP, mean SBP, or visit-to-visit SBP variability. CONCLUSIONS: Longer TIR is associated with lower cardiovascular risk and may add value as an outcome measure for hypertension control studies among patients with diabetes.

Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure.

Importance: Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population. Objectives: To estimate the time to benefit from SGLT2 inhibitors among patients with HF. Design, Setting, and Participants: This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022. Intervention: Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials. Results: Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction. Conclusions and Relevance: In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

Alignment-free genome comparison with feature frequency profiles (FFP) and optimal resolutions.

For comparison of whole-genome (genic + nongenic) sequences, multiple sequence alignment of a few selected genes is not appropriate. One approach is to use an alignment-free method in which feature (or l-mer) frequency profiles (FFP) of whole genomes are used for comparison-a variation of a text or book comparison method, using word frequency profiles. In this approach it is critical to identify the optimal resolution range of l-mers for the given set of genomes compared. The optimum FFP method is applicable for comparing whole genomes or large genomic regions even when there are no common genes with high homology. We outline the method in 3 stages: (i) We first show how the optimal resolution range can be determined with English books which have been transformed into long character strings by removing all punctuation and spaces. (ii) Next, we test the robustness of the optimized FFP method at the nucleotide level, using a mutation model with a wide range of base substitutions and rearrangements. (iii) Finally, to illustrate the utility of the method, phylogenies are reconstructed from concatenated mammalian intronic genomes; the FFP derived intronic genome topologies for each l within the optimal range are all very similar. The topology agrees with the established mammalian phylogeny revealing that intron regions contain a similar level of phylogenic signal as do coding regions.

Whole-proteome phylogeny of large dsDNA virus families by an alignment-free method.

The vast sequence divergence among different virus groups has presented a great challenge to alignment-based sequence comparison among different virus families. Using an alignment-free comparison method, we construct the whole-proteome phylogeny for a population of viruses from 11 viral families comprising 142 large dsDNA eukaryote viruses. The method is based on the feature frequency profiles (FFP), where the length of the feature (l-mer) is selected to be optimal for phylogenomic inference. We observe that (i) the FFP phylogeny segregates the population into clades, the membership of each has remarkable agreement with current classification by the International Committee on the Taxonomy of Viruses, with one exception that the mimivirus joins the phycodnavirus family; (ii) the FFP tree detects potential evolutionary relationships among some viral families; (iii) the relative position of the 3 herpesvirus subfamilies in the FFP tree differs from gene alignment-based analysis; (iv) the FFP tree suggests the taxonomic positions of certain "unclassified" viruses; and (v) the FFP method identifies candidates for horizontal gene transfer between virus families.