Боровикова Ирина Ивановна
Факультет компьютерных наук
Должности
- Стажер-исследователь — Факультет компьютерных наук, Институт искусственного интеллекта и цифровых наук, Центр биомедицинских исследований и технологий
Био
- · Начала работать в НИУ ВШЭ в 2026 году.
Образование
- 2025 · Специалитет: Московский государственный университет им. М.В. Ломоносова, специальность «Биоинженерия и биоинформатика», квалификация «Биоинженер и биоинформатик»
Опыт работы
- · 2025 - н.в.: : стажер-исследователь, Международная лаборатория биоинформатики НИУ ВШЭ
Публикации (2)
Molecular dynamics simulations refine the pathogenicity of ACVRL1 kinase domain variants by quantifying impacts on ATP binding in pulmonary arterial hypertension
2026 · ARTICLE · en
Single amino acid substitutions in the ATP-binding domain of ACVRL1, a key receptor in the bone morphogenetic protein (BMP) signaling pathway, are frequently classified as variants of uncertain significance (VUS), complicating molecular diagnosis for pulmonary arterial hypertension (PAH) and Hereditary Hemorrhagic Telangiectasia (HHT). Since aberrant ATP binding disrupts downstream SMAD1/5/8 phosphorylation, we employed molecular dynamics (MD) simulations to quantitatively assess the functional impact of these variants. We first validated our approach on 20 known pathogenic/likely pathogenic variants within 5Å of the ATP-binding site, finding that 18 (90%) caused significant alterations in binding affinity (|d| ≥ 0.8, p in silico mutagenesis of all possible substitutions at ATP-binding pocket positions, combined with InterVar classification under HHT phenotype, enabled reclassification of 9 of 12 (75%) VUS as likely pathogenic. Finally, we demonstrated the applicability of this approach in two PAH patients with HHT carrying ACVRL1 VUS. This work establishes MD simulation of ATP-binding affinity as an effective and scalable tool for the functional interpretation of kinase variants, with broad potential for application across other disease-associated kinases.
The prevalence of pathogenic variants in the BMPR2 gene in patients with the idiopathic pulmonary arterial hypertension in the Russian population: sequencing data and meta-analysis
2025 · ARTICLE · en
Background Idiopathic pulmonary arterial hypertension (IPAH) is a rare and severe form of pulmonary hypertension, with a genetic basis most commonly associated with mutations in the BMPR2 gene. However, no genetic testing has been reported for IPAH patients in the Russian population, nor have systematic studies been conducted to assess the frequency of pathogenic variants in this group. Methods The study cohort included 105 IPAH patients, consisting of 23 males and 82 females, who were managed at the PH care center in Moscow, Russia, from 2014 to 2024. Genetic testing was performed using whole-genome sequencing. Variant identification and annotation were conducted using GATK, DeepVariant, VEP, sv-callers and AnnotSV. A meta-analysis, performed with MOOSE, included 24 studies involving 3124 IPAH patients and 470 P/LP variants. Pathogenicity reassessment was carried out using InterVar, which incorporates ACMG criteria. Results Analysis of 105 adult IPAH patients in Russia revealed 11 patients (10.48%) as carriers of pathogenic or likely pathogenetic (P/LP) BMPR2 variants. As the result of reassessment, the number of P/LP BMPR2 variants raised from 394 (59%) to 445 (67%) with 80 pathogenic variants became of uncertain significance, and 152 unclassified variants became P/LP. The meta-analysis of these reevaluated pathogenic variants showed that while the frequency of P/LP variants in our cohort (10.48%) is lower than the overall average of 17.75% from the meta-analysis, the difference is not statistically significant (p = 0.062). Additionally, we report three P/LP BMPR2 variants, not reported in literature, with one being structural, and four P/LP variants in TBX4, ATP13A3 and AQP1 genes from 27 IPAH genes in 3 patients. Conclusions For the first time, we present the results of genetic testing in IPAH patients from the Russian population. Despite the considerable heterogeneity in the world-wide data, the prevalence of pathogenic BMPR2 mutations in IPAH patients from the Russian population does not significantly differ from the overall average in the meta-analysis. It is crucial to periodically reassess the pathogenicity of published variants, as half of the pathogenic BMPR2 IPAH variants were reclassified as LP or of uncertain significance.
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