OBJECTIVE The subtraction of lumbar lordosis (LL) from the pelvic incidence (PI) offers an estimate of the LL required for a given PI value. Relative LL (RLL) and the lordosis distribution index (LDI) are PI-based individualized measures. RLL quantifies the magnitude of lordosis relative to the ideal lordosis as defined by the magnitude of PI. LDI defines the magnitude of lower arc lordosis in proportion to total lordosis. The aim of this study was to compare RLL and PI - LL for their ability to predict postoperative complications and their correlations with health-related quality of life (HRQOL) scores. METHODS Inclusion criteria were ≥ 4 levels of fusion and ≥ 2 years of follow-up. Mechanical complications were proximal junctional kyphosis/proximal junctional failure, distal junctional kyphosis/distal junctional failure, rod breakage, and implant-related complications. Correlations between PI - LL, RLL, PI, and HRQOL were analyzed using the Pearson correlation coefficient. Mechanical complication rates in PI - LL, RLL, LDI, RLL, and LDI interpreted together, and RLL subgroups for each PI - LL category were compared using chi-square tests and the exact test. Predictive models for mechanical complications with RLL and PI - LL were analyzed using binomial logistic regressions. RESULTS Two hundred twenty-two patients (168 women, 54 men) were included. The mean age was 52.2 ± 19.3 years (range 18-84 years). The mean follow-up was 28.8 ± 8.2 months (range 24-62 months). There was a significant correlation between PI - LL and PI (r = 0.441, p < 0.001), threatening the use of PI - LL to quantify spinopelvic mismatch for different PI values. RLL was not correlated with PI (r = -0.093, p > 0.05); therefore, it was able to quantify divergence from ideal lordosis for all PI values. Compared with PI - LL, RLL had stronger correlations with HRQOL scores (p < 0.05). Discrimination performance was better for the model with RLL than for PI - LL. The agreement between RLL and PI - LL was high (κ = 0.943, p < 0.001), moderate (κ = 0.455, p < 0.001), and poor (κ = -0.154, p = 0.343), respectively, for large, average, and small PI sizes. When analyzed by RLL, each PI - LL category was further divided into distinct groups of patients who had different mechanical complication rates (p < 0.001). CONCLUSIONS Using the formula of PI - LL may be insufficient to quantify normolordosis for the whole spectrum of PI values when applied as an absolute numeric value in conjunction with previously reported population-based average thresholds of 10° and 20°. Schwab PI - LL groups were found to constitute an inhomogeneous group of patients. RLL offers an individualized quantification of LL for all PI sizes. Compared with PI - LL, RLL showed a greater association with both mechanical complications and HRQOL. The use of RLL and LDI together, instead of PI - LL, for surgical planning may result in lower mechanical complication rates and better long-term HRQOL.

Lumbar lordosis

Kyphosis

10.3171/2017.8.focus17498

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Citations (94)

Intrinsic Dynamics and Causality in Correlated Motions Unraveled in Two Distinct Inactive States of Human β₂-Adrenergic Receptor

The Journal of Physical Chemistry B (2019)

Nuray Söğünmez Ebru Demet Akten

The alternative inactive state of the human β2-adrenergic receptor originally exposed in molecular dynamics simulations was investigated using various analysis tools to evaluate causality between correlated residue-pair fluctuations and suggest allosteric communication pathways. A major conformational shift observed in the third intracellular loop (ICL3) displayed a novel inactive state, featuring an inaccessible G protein binding site blocked by ICL3 and an expanded orthosteric ligand binding site. Residue-based mean-square fluctuation and stiffness calculations revealed a significant mobility decrease in ICL3, which induced a mobility increase in the remaining loop regions. This indicates conformational entropy loss in one mobile region being compensated by residual intermolecular motions in other mobile regions. Moreover, the extent of significantly correlated motions decreased, and correlations that once existed between transmembrane helices shifted toward regions with increased mobility. Conditional time-delayed cross-correlation analysis identified distinct driver–follower relationship profiles. Prior to its packing, freely moving ICL3 was markedly driven by transmembrane helix-8 whereas once packed, ICL3 controlled future fluctuations of nearby helices. Moreover, two transmembrane helices, (H5 and H6), started to control future fluctuations of a remote site, the extracellular loop, ECL2. This clearly suggests that allosteric coupling between extra- and intracellular parts intensified, in agreement with the receptor's well recognized feature, which is the inverse proportionality between activity and the degree of coupling.

Causality

Dynamics

10.1021/acs.jpcb.9b01202

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Citations (3)

Global Alignment and Proportion (GAP) Score

Journal of Bone and Joint Surgery (2017)

Çağlar Yılgör Nuray Söğünmez Louis Boissière Yasemin Yavuz Ibrahim Obeid

Background: The restoration of normal sagittal alignment is a critical goal in adult spinal deformity surgery to achieve favorable outcomes and prevent mechanical complications. Schwab sagittal modifiers have been accepted as targets for appropriate alignment, but addressing these targets does not always prevent high mechanical complication or revision rates. This may be because the linear absolute numerical parameters do not cover the whole pelvic incidence spectrum and the distribution of lordosis, pelvic anteversion, and negative malalignment are not considered as potential causes of failure. The aim of the present study was to develop and validate a score based on pelvic-incidence-based proportional parameters to better predict mechanical complications. Methods: Two hundred and twenty-two patients (168 women and 54 men) followed for ≥2 years after posterior fusion at ≥4 levels were included in the study. The mean age (and standard deviation) was 52.2 ± 19.3 years (range, 18 to 84 years), and the mean duration of follow-up was 28.8 ± 8.2 months (range, 24 to 62 months). The global alignment and proportion (GAP) score was developed and validated in groups of patients randomly assigned to derivation (n = 148, 66.7%) and validation (n = 74, 33.3%) cohorts. GAP score parameters were relative pelvic version (the measured minus the ideal sacral slope), relative lumbar lordosis (the measured minus the ideal lumbar lordosis), lordosis distribution index (the L4-S1 lordosis divided by the L1-S1 lordosis multiplied by 100), relative spinopelvic alignment (the measured minus the ideal global tilt), and an age factor. Proximal and distal junctional kyphosis and/or failure, rod breakage, and other implant-related complications were considered mechanical complications. The predictive accuracy of the GAP score was analyzed using receiver operating characteristic (ROC) analyses. Associations between GAP categories and mechanical complications and revisions were analyzed using Cochran-Armitage tests. Results: In the validation cohort, 32 patients (43%) experienced mechanical complications and 17 (23%) underwent mechanical revision. The area under curve for the GAP score predicting mechanical complications was 0.92 (standard error [SE] = 0.034, p < 0.001, 95% [confidence interval [CI] = 0.85 to 0.98). Postoperatively, patients with a proportioned spinopelvic state according to the GAP score had a mechanical complication rate of 6% while those with a moderately or severely disproportioned spinopelvic state had rates of 47% and 95%, respectively. Conclusions: The GAP score is a new pelvic-incidence-based proportional method of analyzing the sagittal plane that predicts mechanical complications in patients undergoing surgery for adult spinal deformity. Setting surgical goals according to the GAP score may decrease the prevalence of mechanical complications.

Pelvic tilt

Lumbar lordosis

Spinal Deformity

10.2106/jbjs.16.01594

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Citations (458)

Deciphering the Cluster-Specific Marker Genes via Integration of Single Cell RNA Sequencing Datasets

2022 Innovations in Intelligent Systems and Applications Conference (ASYU) (2023)

Wardah Afzal Rinch Nuray Söğünmez Aiman Altaf Hüseyin Fuat Alsan Taner Arsan

Experimental data from brain tissues are critical for tackling the problems in brain development and revealing the underlying mechanisms of disease states. However, obtaining the brain tissue is a major challenge. Human brain organoids hold remarkable promise for this goal, but they suffer from substantial organoid-to-organoid variability. We performed a data-driven analysis on single-cell RNA-sequencing data using 17775 cells isolated from 2 individual organoids. The main goal was to accurately integrate the data coming from unmatched datasets, cluster the cells based on their similarity levels and predict the differentially expressed genes per cell types to reveal novel brain cell types and markers. This research opens a way to map human brain cells and develop novel and precise machine learning algorithms for accurate scRNA-Seq data analysis.

Organoid

Human brain

Brain Cell

Cell type

Brain tissue

Similarity (geometry)

10.1109/asyu58738.2023.10296679

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Information Transfer in Active States of Human β2-Adrenergic Receptor via Inter-Rotameric Motions of Loop Regions

Applied Sciences (2022)

Nuray Söğünmez Ebru Demet Akten

Two independent 1.5 μs long MD simulations were conducted for the fully atomistic model of the human beta2-adrenergic receptor (β2AR) in a complex with a G protein to investigate the signal transmission in a fully active state via mutual information and transfer entropy based on α-carbon displacements and rotameric states of backbone and side-chain torsion angles. Significant correlations between fluctuations in α-Carbon displacements were mostly detected between transmembrane (TM) helices, especially TM5 and TM6 located at each end of ICL3 and TM7. Signal transmission across β2-AR was quantified by shared mutual information; a high amount of correspondence was distinguished in almost all loop regions when rotameric states were employed. Moreover, polar residues, especially Arg, made the most contribution to signal transmission via correlated side-chain rotameric fluctuations as they were more frequently observed in loop regions than hydrophobic residues. Furthermore, transfer entropy identified all loop regions as major entropy donor sites, which drove future rotameric states of torsion angles of residues in transmembrane helices. Polar residues appeared as donor sites from which entropy flowed towards hydrophobic residues. Overall, loops in β2AR were recognized as potential allosteric hot spot regions, which play an essential role in signal transmission and should likely be used as potential drug targets.

Side chain

10.3390/app12178530

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Citations (2)

Global Alignment and Proportion (GAP) Score: Development and Validation of a New Method of Analyzing Spinopelvic Alignment to Predict Mechanical Complications After Adult Spinal Deformity Surgery

The Spine Journal (2017)

Çağlar Yılgör Nuray Söğünmez Yasemin Yavuz Louis Boissière Ibrahim Obeid

Spinal Deformity

Lumbar lordosis

10.1016/j.spinee.2017.07.234

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Citations (61)

Sparse deconvolution of cell type medleys in spatial transcriptomics

bioRxiv (Cold Spring Harbor Laboratory) (2025)

Nuray Söğünmez Deniz Eroğlu

Mapping cell distributions across spatial locations with whole-genome coverage is essential for understanding cellular responses and signaling pathways. However, current deconvolution models often assume strong overlap between reference and spatial datasets, neglecting biological constraints like sparsity and cell-type variations. As a result, these methods rely on brute-force algorithms that ignore tissue complexity, leading to inaccurate predictions, particularly in heterogeneous or unmatched datasets. We introduce Weight-Induced Sparse Regression (WISpR), a machine learning algorithm that integrates spot-specific hyperparameters and sparsity-driven modeling. Unlike brute-force methods, WISpR accurately predicts cell-type distributions while maintaining biological coherence, even in unmatched datasets. Benchmarking against five leading methods across ten datasets, WISpR consistently outperformed competitors and predicted cellular landscapes in both normal and cancerous tissues. By leveraging sparse cell-type arrangements, WISpR provides biologically informed, high-resolution cellular maps. Its ability to decode tissue organization in both healthy and diseased states marks a major advancement in spatial transcriptomics, setting a new standard for accurate deconvolution.

10.1101/2025.02.07.637009

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Konjenital Skolyoz Tanı ve Tedavisi

Acibadem Universitesi Saglik Bilimleri Dergisi (2019)

Çağlar Yılgör İrem Nur Eroğlu Nuray Söğünmez Kadir Abul Ahmet Alanay

Congenital scoliosis is the most common congenital spinal deformity caused by a failure in the formation or segmentation or both. Clinical manifestations may vary from stable hemivertebra to complex deformities that can lead to pulmonary, cardiac, genitourinary and neurological complications. Other system anomalies may accompany as well. Prenatal ultrasound, physical examination and x-rays are used for diagnosis. MR is helpful in detecting accompanying pathologies. CT may be useful in preoperative planning. The treatment plan is tailored to each patient according to location and magnitude of the curve, patient age, type of the deformity and the anticipated natural history. Treatment consists of controlled observation, conservative and surgical methods. Hemivertebrectomy and limited fusion are recommended at an early age for single hemivertebra. Hemiepiphysiodesis, distraction-based non-fusion methods or combinations of these may be used for more complex deformities. Technological advances today allow for concurrent surgeries for spinal deformity and intradural pathologies. Corrective osteotomies may be required in neglected severe cases. Due to the challenging technique and risk of neurological injury, corrective osteotomies necessitate well-equipped centers and experienced surgeons

10.31067/0.2019.137

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Relative Lumbar Lordosis (RLL): a New PI-Based Proportional Parameter that Quantifies Lumbar Lordosis More Precisely Compared to PI-LL Concept

The Spine Journal (2017)

Çağlar Yılgör Nuray Söğünmez Yasemin Yavuz Louis Boissière Ibrahim Obeid

Lumbar lordosis

10.1016/j.spinee.2017.08.138

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