Search bioRxiv⌕ Search

Biology subjects

Stankovic, A.

Publications and source records attributed to Stankovic, A..

3 recordsLinked to original sources

The Principal Component Life Trajectory (PCLT): Mapping Sex-Specific Physiological Change Across the Human Lifespan

Age- and sex-related variation in physiological biomarkers is well documented, yet how coordinated systemic physiology unfolds across life stages at the population level remains unclear. Here, we introduce the Principal Component Life Trajectory (PCLT), reconstructing physiological trajectories via multivariate analysis of 54 blood-based biomarkers from 11,124 participants in the National Health and Nutrition Examination Survey (NHANES). Quantifying year-on-year progression with Euclidean Trajectory Distance (ETD), we identify five distinct phases in an unbiased manner: Early adolescence, Sexual Divergence, Sexual Convergence, Late Adulthood, and Advanced Aging. Trajectories show early, pronounced sexual divergence validated in an ethnically distinct, independent cohort. Chronic disease is associated with PCLT displacement and increased ETD progression, whereas metabolic, behavioral, and psychosocial factors generate graded, phase-specific perturbations. Together, these findings establish PCLT as a reproducible framework for characterizing structured physiological change across the lifespan and for monitoring population-level health dynamics.

systems biology↗

Co-option of CENP-A for activity-induced neuronal plasticity

Neuronal activation drives activity-dependent gene expression that underlies experience-associated synaptic modifications, learning and memory. Here we show that the histone variant CENP-A, best known for specifying centromere identity, is dynamically regulated by synaptic activity at both the RNA and protein levels in postmitotic neurons. Neuronal activation increases a non-centromeric nuclear pool of CENP-A while leaving centromeric CENP-A levels unchanged. Downregulation of CENP-A selectively reduces the activity-associated non-centromeric pool, impairs activity-dependent induction of immediate-early genes such as FOS and ARC, and disrupts hippocampus-dependent learning and memory. Furthermore, we find that activity-dependent neuronal responses in human embryonic stem cell-derived forebrain organoids similarly require CENP-A. Our results reveal a mitosis-independent, conserved role of CENP-A for driving plasticity in mammalian neurons.

neuroscience↗

Benchmarking challenging small variants with linked and long reads

Genome in a Bottle (GIAB) benchmarks have been widely used to help validate clinical sequencing pipelines and develop new variant calling and sequencing methods. Here, we use accurate linked reads and long reads to expand the prior benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are not readily accessible to short reads. Our new benchmark adds more than 300,000 SNVs, 50,000 indels, and 16 % new exonic variants, many in challenging, clinically relevant genes not previously covered (e.g., PMS2). For HG002, we include 92% of the autosomal GRCh38 assembly, while excluding problematic regions for benchmarking small variants (e.g., copy number variants and reference errors) that should not have been in the previous version, which included 85% of GRCh38. By including difficult-to-map regions, this benchmark identifies eight times more false negatives in a short read variant call set relative to our previous benchmark.We have demonstrated the utility of this benchmark to reliably identify false positives and false negatives across technologies in more challenging regions, which enables continued technology and bioinformatics development.

genomics↗