Integration of Hi-C with short and long-read genome sequencing reveals the structure of germline rearranged genomes.

Structural variants are a common cause of disease and contribute to a large extent to inter-individual variability, but their detection and interpretation remain a challenge. Here, we investigate 11 individuals with complex genomic rearrangements including germline chromothripsis by combining short- and long-read genome sequencing (GS) with Hi-C. Large-scale genomic rearrangements are identified in Hi-C interaction maps, allowing for an independent assessment of breakpoint calls derived from the GS methods, resulting in >300 genomic junctions. Based on a comprehensive breakpoint detection and Hi-C, we achieve a reconstruction of whole rearranged chromosomes. Integrating information on the three-dimensional organization of chromatin, we observe that breakpoints occur more frequently than expected in lamina-associated domains (LADs) and that a majority reshuffle topologically associating domains (TADs). By applying phased RNA-seq, we observe an enrichment of genes showing allelic imbalanced expression (AIG) within 100 kb around the breakpoints. Interestingly, the AIGs hit by a breakpoint (19/22) display both up- and downregulation, thereby suggesting different mechanisms at play, such as gene disruption and rearrangements of regulatory information. However, the majority of interpretable genes located 200 kb around a breakpoint do not show significant expression changes. Thus, there is an overall robustness in the genome towards large-scale chromosome rearrangements.

WCTECGdb: A 12-Lead Electrocardiography Dataset Recorded Simultaneously with Raw Exploring Electrodes' Potential Directly Referred to the Right Leg.

With this paper we communicated the existence of a surface electrocardiography (ECG) recordings dataset, named WCTECGdb, that aside from the standard 12-lead signals includes the raw electrode biopotential for each of the nine exploring electrodes refereed directly to the right leg. This dataset, comprises of 540 ten second segments recorded from 92 patients at Campbelltown Hospital, NSW Australia, and is now available for download from the Physionet platform. The data included in the dataset confirm that the Wilson's Central Terminal (WCT) has a relatively large amplitude (up to 247% of lead II) with standard ECG characteristics such as a p-wave and a t-wave, and is highly variable during the cardiac cycle. As further examples of application for our data, we assess: (1) the presence of a conductive pathway between the legs and the heart concluding that in some cases is electrically significant and (2) the initial assumption about the limbs potential stating the dominance of the left arm concluding that this is not always the case and that might requires case to case assessment.

Towards Real-Time Heartbeat Classification: Evaluation of Nonlinear Morphological Features and Voting Method.

Abnormal heart rhythms are one of the significant health concerns worldwide. The current state-of-the-art to recognize and classify abnormal heartbeats is manually performed by visual inspection by an expert practitioner. This is not just a tedious task; it is also error prone and, because it is performed, post-recordings may add unnecessary delay to the care. The real key to the fight to cardiac diseases is real-time detection that triggers prompt action. The biggest hurdle to real-time detection is represented by the rare occurrences of abnormal heartbeats and even more are some rare typologies that are not fully represented in signal datasets; the latter is what makes it difficult for doctors and algorithms to recognize them. This work presents an automated heartbeat classification based on nonlinear morphological features and a voting scheme suitable for rare heartbeat morphologies. Although the algorithm is designed and tested on a computer, it is intended ultimately to run on a portable i.e., field-programmable gate array (FPGA) devices. Our algorithm tested on Massachusetts Institute of Technology- Beth Israel Hospital(MIT-BIH) database as per Association for the Advancement of Medical Instrumentation(AAMI) recommendations. The simulation results show the superiority of the proposed method, especially in predicting minority groups: the fusion and unknown classes with 90.4% and 100%.

Minimization of the Wilson's Central Terminal voltage potential via a genetic algorithm.

OBJECTIVE: The Wilson Central Terminal (WCT) is an artificially constructed reference for surface electrocardiography, which is assumed to be near zero and steady during the cardiac cycle; namely it is the simple average of the three recorded limbs (right arm, left arm and left leg) composing the Einthoven triangle and considered to be electrically equidistant from the electrical center of the heart. This assumption has been challenged and disproved in 1954 with an experiment designed just to measure and minimize WCT. Minimization was attempted varying in real time the weight resistors connected to the limbs. Unfortunately, the experiment required a very cumbersome setup and showed that WCT amplitude could not be universally minimized, in other words, the weight resistors change for each person. Taking advantage of modern computation techniques as well as of a special ECG device that aside of the standard 12-lead Electrocardiogram (ECG) can measure WCT components, we propose a software minimization (genetic algorithm) method using data recorded from 72 volunteers. RESULT: We show that while the WCT presents average amplitude relative to lead II of 58.85% (standard deviation of 30.84%), our minimization method yields an amplitude as small as 7.45% of lead II (standard deviation of 9.04%).

On the Einthoven Triangle: A Critical Analysis of the Single Rotating Dipole Hypothesis.

Since its inception, electrocardiography has been based on the simplifying hypothesis that cardinal limb leads form an equilateral triangle of which, at the center/centroid, the electrical equivalent of the cardiac activity rotates during the cardiac cycle. Therefore, it is thought that the three limbs (right arm, left arm, and left leg) which enclose the heart into a circuit, where each branch directly implies current circulation through the heart, can be averaged together to form a stationary reference (central terminal) for precordials/chest-leads. Our hypothesis is that cardinal limbs do not form a triangle for the majority of the duration of the cardiac cycle. As a corollary, the central point may not lie in the plane identified by the limb leads. Using a simple and efficient algorithm, we demonstrate that the portion of the cardiac cycle where the three limb leads form a triangle is, on average less, than 50%.