AnchorWave: Sensitive alignment of genomes with high sequence diversity, extensive structural polymorphism, and whole-genome duplication

Millions of species are currently being sequenced, and their genomes are being compared. Many of them have more complex genomes than model systems and raise novel challenges for genome alignment. Widely used local alignment strategies often produce limited or incongruous results when applied to genomes with dispersed repeats, long indels, and highly diverse sequences. Moreover, alignment using many-to-many or reciprocal best hit approaches conflicts with well-studied patterns between species with different rounds of whole-genome duplication. Here, we introduce Anchored Wavefront alignment (AnchorWave), which performs whole-genome duplication–informed collinear anchor identification between genomes and performs base pair–resolved global alignment for collinear blocks using a two-piece affine gap cost strategy. This strategy enables AnchorWave to precisely identify multikilobase indels generated by transposable element (TE) presence/absence variants (PAVs). When aligning two maize genomes, AnchorWave successfully recalled 87% of previously reported TE PAVs. By contrast, other genome alignment tools showed low power for TE PAV recall. AnchorWave precisely aligns up to three times more of the genome as position matches or indels than the closest competitive approach when comparing diverse genomes. Moreover, AnchorWave recalls transcription factor–binding sites at a rate of 1.05- to 74.85-fold higher than other tools with significantly lower false-positive alignments. AnchorWave complements available genome alignment tools by showing obvious improvement when applied to genomes with dispersed repeats, active TEs, high sequence diversity, and whole-genome duplication variation.

In-Silico Screening of Prime PCOS Biomarkers for the Identification of a Potential Model Organism

Polycystic ovarian syndrome (PCOS) is a multigenic endocrine disorder observed in women of reproductive age. Although the condition is characterized by the presence of polycystic ovaries and excess production of androgens, the exact aetiology has not been well deciphered due to the unavailability of a suitable model organism. Defects in the two prime biomarkers namely CYP11A and CYP19A1, have been found to play a role in disease progression. The objective of this study was to carry out an in-silico assessment of these two genes to identify a potential model organism for the efficacious study of PCOS. Bioinformatics tools such as BLAST and EMBOSS were used for local and global alignment respectively, to find sequence homology and thereby, establish a model organism. Sequence comparison was followed by phylogenetic analysis and secondary structure prediction of the enzymes encoded by the respective genes. Our in-silico study revealed Gorilla gorilla to be an ideal candidate for the study of PCOS owing to its high sequence and structural similarities with the human gene counterparts. Future prospects of the research include in-vitro analysis of the biomarkers on Gorilla gorilla ovarian theca cell line to pave the way for therapy.

How to Lay Bricks: Local-Global Alignment Predicts Preference for Shifted Tile Patterns

We examine the aesthetic characteristics of row tile patterns defined by repeating strips of polygons. In experiment 1 participants rated the perceived beauty of equilateral triangle, square and rectangular tilings presented at vertical and horizontal orientations. The tiles were shifted by one-fourth increments of a complete row cycle. Shifts that preserved global symmetry were liked the most. Local symmetry by itself did not predict ratings but tilings with a greater number of emergent features did. In a second experiment we presented row tiles using all types of three- and four-sided geometric figures: acute, obtuse, isosceles and right triangles, kites, parallelograms, a rhombus, trapezoid, and trapezium. Once again, local polygon symmetry did not predict responding but measures of correspondence between local and global levels did. In particular, number of aligned polygon symmetry axes and number of aligned polygon sides were significantly and positively correlated with beauty ratings. Preference was greater for more integrated tilings, possibly because they encourage the formation of gestalts and exploration within and across levels of spatial scale.

Paradoxical spinopelvic motion: does global balance influence spinopelvic motion in total hip arthroplasty?

Background Recent research has proposed a classification of spinopelvic stiffness according to pelvic spatial orientation for risk stratification in patients who undergo total hip arthroplasty (THA). However, the influence of global alignment was not investigated, and this study evaluated the effect of global balance (sagittal vertical axis [SVA]) on spinopelvic motion. Methods We conducted a retrospective review of consecutive primary THA patients. We measured SVA, spinopelvic parameters (pelvic tilt [PT], pelvic incidence, and sacral slope), thoracic kyphosis (TK), lumbar lordosis (LL), proximal femur angle (PFA), and cup version using functional radiographs of patients in the standing and upright sitting positions. Linear regression was performed to identify parameters related to global trunk alignment change (∆SVA). Spinopelvic stiffness was defined as PT position change < 10°, and a subset of patients with PT change < 0° was categorized into a paradoxical spinopelvic motion group. Results One hundred twenty-four patients were analyzed (mean age: 65 years, 61% female). In univariate regression analysis, ∆TK, ∆LL, and ∆PFA were correlated to ∆SVA. In multivariate regression analysis, ΔLL (p < 0.001) and ΔPFA (p < 0.001) were found to be correlated to ΔSVA (ΔSVA = − 11.97 + 0.05ΔTK – 0.23ΔLL – 0.17ΔPFA; adjusted R2 = 0.558). Spinopelvic stiffness was observed in 40 patients (32%), including five (4%) with paradoxical motion (∆PT = − 3° ± 1°, p < 0.001) with characteristics of balanced standing global trunk alignment (standing SVA = − 1.0 ± 5.1 cm), similar stiffness of the lumbosacral spine (∆LL = − 7° ± 5°), higher hip motion (∆PFA = − 78° ± 6°, p = 0.017), and higher anterior trunk shift (∆SVA = 6.2 ± 2.0 cm, p = 0.003) from standing to sitting as compared to the stiffness group. Two of these five patients experienced dislocation events after THA. Conclusions The lumbosacral and hip motions were the major contributors to global alignment postural change. Paradoxical motion is a rare but dangerous clinical condition in THA that might be related to a disproportionally large trunk shift in the stiff lumbosacral spine causing excessive hip motion. In paradoxical motion, diminishing functional acetabular clearance during position change might pose the prosthesis at higher risk of impingement and instability than spinopelvic stiffness.

Etiology, diagnosis, and treatment of iatrogenic spinal deformity

Background: Spinal fusion is a common procedure that provides spinal stability by connecting vertebral segments using a bone graft. Because the spinal alignment is fixed permanently after spinal fusion, a mal-aligned fusion can produce iatrogenic spinal deformity and imbalance with significant disability.Current Concepts: Failure to restore adequate segmental lordosis in lumbar spinal fusion is a common cause of iatrogenic spine deformity. Local and regional spinal deformities can affect the global alignment; accordingly, spinal imbalance can occur when the compensation mechanisms fail. Diagnosis and surgical planning should be made on a thorough analysis of global and spinopelvic parameters on the standing whole-spine radiographs. Surgical treatment includes neural decompression, spinal fusion, and deformity correction. Spinal osteotomy provides a favorable surgical outcome, although the complication rate is high.Discussion and Conclusion: Iatrogenic spine deformity is increasing due to the increased occurrence of spinal fusion surgery. To prevent iatrogenic spine deformity, the index fusion surgery should be performed based on a comprehensive analysis of spinopelvic alignment and balance.

Clinical Outcomes of S2 Alar-Iliac (S2AI) Screw Technique in The Treatment of Severe Spinal Sagittal Imbalance: A Retrospective 2-Year Follow-Up Study

Background The treatment of adult spinal deformity (ASD) remains a significant challenge, especially in elderly patients. This study aimed to evaluate the outcomes of the S2AI screw technique in the treatment of severe spinal sagittal imbalance with a minimum 2-year follow-up. Methods From January 2015 to December 2018, 23 patients with severe degenerative thoracolumbar kyphosis who underwent placement of S2AI screws for long segment fusion were retrospectively reviewed. Patients were divided into group A (no mechanical complications, 13 cases) and group B (with mechanical complications, 10 cases) according to the occurrence of mechanical complications at the last follow-up. Radiographic parameters were compared between groups preoperatively, 1 month postoperatively, and at the last follow-up. Risk factors for mechanical complications were analyzed. Results The incidence of mechanical complications was 43.5%, and the revision rate was 17.4%. At 1 month postoperatively, sagittal correction was better in group A than in group B (P<0.05). The lumbar lordosis (LL), pelvic incidence minus lumbar lordosis (PI-LL), T1 pelvic angle (TPA), and sagittal vertical axis (SVA) of both groups at the last follow-up were significantly different from corresponding values at 1 month postoperatively (P<0.05), and the sagittal correction was partially lost. Pearson correlation analysis revealed that the occurrence of mechanical complications was associated with sacral slope (SS), LL, PI-LL, and global alignment and proportion (GAP) score at 1 month postoperatively. Conclusion A high incidence of mechanical complications was observed in long-segment corrective surgery with the S2AI screw technique for severe spinal sagittal imbalance. Inadequate sagittal correction is a risk factor for the development of mechanical complications.

When can we expect global sagittal alignment to reach a stable value following cervical deformity surgery?

OBJECTIVE Cervical deformity (CD) is a complex condition with a clear impact on patient quality of life, which can be improved with surgical treatment. Previous study following thoracolumbar surgery demonstrated a spontaneous and maintained improvement in cervical alignment following lumbar pedicle subtraction osteotomy (PSO). In this study the authors aimed to investigate the complementary questions of whether cervical alignment induces a change in global alignment and whether this change stabilizes over time. METHODS To analyze spontaneous changes, this study included only patients with at least 5 levels remaining unfused following surgery. After data were obtained for the entire cohort, repeated-measures analyses were conducted between preoperative baseline and 3-month and 1-year follow-ups with a post hoc analysis and Bonferroni correction. A subanalysis of patients with 2-year follow-up was performed. RESULTS One-year follow-up data were available for 121 of 168 patients (72%), and 89 patients had at least 5 levels remaining unfused following surgery. Preoperatively there was a moderate anterior cervical alignment (C2–7, −7.7° [kyphosis]; T1 slope minus cervical lordosis, 37.1°; cervical sagittal vertebral axis [cSVA], 37 mm) combined with a posterior global alignment (SVA, −8 mm) with lumbar hyperextension (pelvic incidence [PI] minus lumbar lordosis [LL] mismatch [PI-LL], −0.6°). Patients underwent a significant correction of the cervical alignment (median ΔC2–7, 13.6°). Simultaneously, PI-LL, T1 pelvic angle (TPA), and SVA increased significantly (all p < 0.05) between baseline and 3-month and 1-year follow-ups. Post hoc analysis demonstrated that all of the changes occurred between baseline and 3 months. Subanalysis of patients with complete 2-year follow-up demonstrated similar results, with stable postoperative thoracolumbar alignment achieved at 3 months. CONCLUSIONS Correction of cervical malalignment can have a significant impact on thoracolumbar regional and global alignment. Peak relaxation of compensatory mechanisms is achieved by the 3-month follow-up and tends to remain stable. Subanalysis with 2-year data further supports this finding. These findings can help to identify when the results of cervical surgery on global alignment can be best evaluated.

Personalized Federated Learning for ECG Classification Based on Feature Alignment

Electrocardiogram (ECG) data classification is a hot research area for its application in medical information processing. However, insufficient data, privacy preserve, and local deployment are still challenging difficulties. To address these problems, a novel personalized federated learning method for ECG classification is proposed in this paper. First, a global model is trained with federated learning framework on multiple local data clients. Then, we use the global model and private data to train the local model. To reduce the feature inconsistency between global and private local data and for better fitting the private local data, a novel ”feature alignment” module is devised to guarantee the uniformity, which contains two parts, global alignment and local alignment, respectively. For global alignment, the graph metric of batch data is used to constrain the dissimilarity between features generated by the global model and local model. For local alignment, triplet loss is adopted to increase discriminative ability for local private data. Comprehensive experiments on our collected dataset are evaluated. The results show that the proposed method can be better adapted to local data and exhibit superior ability of generalization.