Supertree methods construct trees on a set of taxa (species) combining many smaller trees on the overlapping subsets of the entire set of taxa. A ‘quartet’ is an unrooted tree over taxa, hence the quartet-based supertree methods combine many -taxon unrooted trees into a single and coherent tree over the complete set of taxa. Quartet-based phylogeny reconstruction methods have been receiving considerable attentions in the recent years. An accurate and efficient quartet-based method might be competitive with the current best phylogenetic tree reconstruction methods (such as maximum likelihood or Bayesian MCMC analyses), without being as computationally intensive. In this paper, we present a novel and highly accurate quartet-based phylogenetic tree reconstruction method. We performed an extensive experimental study to evaluate the accuracy and scalability of our approach on both simulated and biological datasets.

Cardiovascular diseases are one of the most severe causes of mortality, annually taking a heavy toll on lives worldwide. Continuous monitoring of blood pressure seems to be the most viable option, but this demands an invasive process, introducing several layers of complexities and reliability concerns due to non-invasive techniques not being accurate. This motivates us to develop a method to estimate the continuous arterial blood pressure (ABP) waveform through a non-invasive approach using Photoplethysmogram (PPG) signals. We explore the advantage of deep learning, as it would free us from sticking to ideally shaped PPG signals only by making handcrafted feature computation irrelevant, which is a shortcoming of the existing approaches. Thus, we present PPG2ABP, a two-stage cascaded deep learning-based method that manages to estimate the continuous ABP waveform from the input PPG signal with a mean absolute error of 4.604 mmHg, preserving the shape, magnitude, and phase in unison. However, the more astounding success of PPG2ABP turns out to be that the computed values of Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), and Systolic Blood Pressure (SBP) from the estimated ABP waveform outperform the existing works under several metrics (mean absolute error of 3.449 ± 6.147 mmHg, 2.310 ± 4.437 mmHg, and 5.727 ± 9.162 mmHg, respectively), despite that PPG2ABP is not explicitly trained to do so. Notably, both for DBP and MAP, we achieve Grade A in the BHS (British Hypertension Society) Standard and satisfy the AAMI (Association for the Advancement of Medical Instrumentation) standard.

Significance: Recent large-scale sequencing efforts have enabled the detection of millions of missense variants. Elucidating their functional effect is of crucial importance but challenging. We approach this problem by performing a wide-scale characterization of missense variants from 1,330 disease-associated genes using >14,000 protein structures. We identify 3D features associated with pathogenic and benign variants that unveiled the mutations’ effect at the molecular level. We further extend our analysis to account for the different essential structural regions in proteins performing different functions. By analyzing variants from 24 gene groups encoding for different protein functional families, we capture function-specific characteristics of missense variants, which match the experimental readouts. We show that our results derived using structural data will effectively inform variant interpretation.