GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.

Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing. We introduce a deep learning framework, GIInger, that identifies GI from HRD-induced scarring observed in low-pass whole-genome sequencing data. GIInger seamlessly integrates into standard BRCA testing workflows and yields reproducible results concordant with a reference method in a multisite study of 327 ovarian cancer samples. Applied to a BRCA wild-type enriched subgroup of 195 PAOLA-1 clinical trial patients, GIInger identified HRD-positive patients who experienced significantly extended progression-free survival when treated with PARPi. GIInger is, therefore, a cost-effective and easy-to-implement method for accurately stratifying patients with ovarian cancer for first-line PARPi treatment.

Finite-size scaling in the Kuramoto model.

We investigate the scaling properties of the order parameter and the largest nonvanishing Lyapunov exponent for the fully locked state in the Kuramoto model with a finite number N of oscillators. We show that, for any finite value of N, both quantities scale as (K-K_{L})^{1/2} with the coupling strength K sufficiently close to the locking threshold K_{L}. We confirm numerically these predictions for oscillator frequencies evenly spaced in the interval [-1,1] and additionally find that the coupling range δK over which this scaling is valid shrinks like δK∼N^{-α} with α≈1.5 as N→∞. Away from this interval, the order parameter exhibits the infinite-N behavior r-r_{L}∼(K-K_{L})^{2/3} proposed by Pazó [Phys. Rev. E 72, 046211 (2005)]PLEEE81539-375510.1103/PhysRevE.72.046211. We argue that the crossover between the two behaviors occurs because at the locking threshold, the upper bound of the continuous part of the spectrum of the fully locked state approaches zero as N increases. Our results clarify the convergence to the N→∞ limit in the Kuramoto model.

Linear stability and the Braess paradox in coupled-oscillator networks and electric power grids.

We investigate the influence that adding a new coupling has on the linear stability of the synchronous state in coupled-oscillator networks. Using a simple model, we show that, depending on its location, the new coupling can lead to enhanced or reduced stability. We extend these results to electric power grids where a new line can lead to four different scenarios corresponding to enhanced or reduced grid stability as well as increased or decreased power flows. Our analysis shows that the Braess paradox may occur in any complex coupled system, where the synchronous state may be weakened and sometimes even destroyed by additional couplings.

Evidence for columnar order in the fully frustrated transverse field Ising model on the square lattice.

Using extensive classical and quantum Monte Carlo simulations, we investigate the ground-state phase diagram of the fully frustrated transverse field Ising model on the square lattice. We show that pure columnar order develops in the low-field phase above a surprisingly large length scale, below which an effective U(1) symmetry is present. The same conclusion applies to the quantum dimer model with purely kinetic energy, to which the model reduces in the zero-field limit, as well as to the stacked classical version of the model. By contrast, the 2D classical version of the model is shown to develop plaquette order. Semiclassical arguments show that the transition from plaquette to columnar order is a consequence of quantum fluctuations.