Targeted DNA-seq and RNA-seq of Reference Samples with Short-read and Long-read Sequencing.

Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions.

A new SU(2/1) supergroup with determinant 1 explains many mysteries of the weak interactions.

Taken as a classification paradigm completing the standard model, a new compact form of the SU(2/1) supergroup explains many mysterious properties of the weak interactions: the maximal breaking of parity, the fractional charges of the quarks, the cancellation of the quantum field theory anomalies, and ties together the existence of the right neutrinos and of the heavier Fermions. This compact supergroup is constructed by exponentiating the matrices representing the leptons and the quarks which form a semi-direct sum of Kac modules of the real superalgebra su(2/1,R) such that the overall trace of the $U(1)$ weak-hypercharge $Y$ vanishes. Remarkably, all the elements of this supergroup have Berezinian 1 and determinant 1.

Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses.

The advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery.

Quartet RNA reference materials improve the quality of transcriptomic data through ratio-based profiling.

Certified RNA reference materials are indispensable for assessing the reliability of RNA sequencing to detect intrinsically small biological differences in clinical settings, such as molecular subtyping of diseases. As part of the Quartet Project for quality control and data integration of multi-omics profiling, we established four RNA reference materials derived from immortalized B-lymphoblastoid cell lines from four members of a monozygotic twin family. Additionally, we constructed ratio-based transcriptome-wide reference datasets between two samples, providing cross-platform and cross-laboratory 'ground truth'.

SU(2/1) superchiral self-duality: a new quantum, algebraic and geometric paradigm to describe the electroweak interactions.

We propose an extension of the Yang-Mills paradigm from Lie algebras to internal chiral superalgebras. We replace the Lie algebra-valued connection one-form , by a superalgebra-valued polyform mixing exterior-forms of all degrees and satisfying the chiral self-duality condition , where denotes the superalgebra grading operator. This superconnection contains Yang-Mills vectors valued in the even Lie subalgebra, together with scalars and self-dual tensors valued in the odd module, all coupling only to the charge parity CP-positive Fermions.

Chirality, a new key for the definition of the connection and curvature of a Lie-Kac superalgebra.

A natural generalization of a Lie algebra connection, or Yang-Mills field, to the case of a Lie-Kac superalgebra, for example SU(m/n), just in terms of ordinary complex functions and differentials, is proposed. Using the chirality which defines the supertrace of the superalgebra: , we construct a covariant differential: , where A is the standard even Lie-subalgebra connection 1-form and a scalar field valued in the odd module. Despite the fact that is a scalar, anticomtes with ( ) because anticommutes with the odd generators hidden in .

Scalar anomaly cancellation reveals the hidden superalgebraic structure of the quantum chiral SU(2/1) model of leptons and quarks.

At the classical level, the SU(2/1) superalgebra offers a natural description of the elementary particles: leptons and quarks massless states, graded by their chirality, fit the smallest irreducible representations of SU(2/1). Our new proposition is to pair the left/right space-time chirality with the superalgebra chirality and to study the model at the one-loop quantum level. If, despite the fact that they are non-Hermitian, we use the odd matrices of SU(2/1) to minimally couple an oriented complex Higgs scalar field to the chiral Fermions, novel anomalies occur.

Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.

Background: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S.

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.

In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling.

Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling.

Dynorphin and Enkephalin Opioid Peptides and Transcripts in Spinal Cord and Dorsal Root Ganglion During Peripheral Inflammatory Hyperalgesia and Allodynia.

Understanding molecular alterations associated with peripheral inflammation is a critical factor in selectively controlling acute and persistent pain. The present report employs in situ hybridization of the 2 opioid precursor mRNAs coupled with quantitative measurements of 2 peptides derived from the prodynorphin and proenkephalin precursor proteins: dynorphin A 1-8 and [Met]-enkephalin-Arg-Gly-Leu. In dorsal spinal cord ipsilateral to the inflammation, dynorphin A 1-8 was elevated after inflammation, and persisted as long as the inflammation was sustained.

Comprehensive Identification and Characterization of Human Secretome Based on Integrative Proteomic and Transcriptomic Data.

Secreted proteins (SPs) play important roles in diverse important biological processes; however, a comprehensive and high-quality list of human SPs is still lacking. Here we identified 6,943 high-confidence human SPs (3,522 of them are novel) based on 330,427 human proteins derived from databases of UniProt, Ensembl, AceView, and RefSeq. Notably, 6,267 of 6,943 (90.

Connections between physics, mathematics, and deep learning.

Starting from Fermat's principle of least action, which governs classical and quantum mechanics and from the theory of exterior differential forms, which governs the geometry of curved manifolds, we show how to derive the equations governing neural networks in an intrinsic, coordinate-invariant way, where the loss function plays the role of the Hamiltonian. To be covariant, these equations imply a layer metric which is instrumental in pretraining and explains the role of conjugation when using complex numbers. The differential formalism clarifies the relation of the gradient descent optimizer with Aristotelian and Newtonian mechanics.

RNA-Seq investigations of human post-mortem trigeminal ganglia.

Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia.

A multi-omic analysis of human naïve CD4+ T cells.

Background: Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases.

Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive.

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

Background: Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model.

Results: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays.

Detecting and correcting systematic variation in large-scale RNA sequencing data.

High-throughput RNA sequencing (RNA-seq) enables comprehensive scans of entire transcriptomes, but best practices for analyzing RNA-seq data have not been fully defined, particularly for data collected with multiple sequencing platforms or at multiple sites. Here we used standardized RNA samples with built-in controls to examine sources of error in large-scale RNA-seq studies and their impact on the detection of differentially expressed genes (DEGs). Analysis of variations in guanine-cytosine content, gene coverage, sequencing error rate and insert size allowed identification of decreased reproducibility across sites.

Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord.

Background: Three neuropeptides, gastrin releasing peptide (GRP), natriuritic precursor peptide B (NPPB), and neuromedin B (NMB) have been proposed to play roles in itch sensation. However, the tissues in which these peptides are expressed and their positions in the itch circuit has recently become the subject of debate. Here we used next-gen RNA-Seq to examine the expression of transcripts coding for GRP, NPPB, NMB, and other peptides in DRG, trigeminal ganglion, and the spinal cord as well as expression levels for their cognate receptors in these tissues.

HIVE-hexagon: high-performance, parallelized sequence alignment for next-generation sequencing data analysis.

Unlabelled: Due to the size of Next-Generation Sequencing data, the computational challenge of sequence alignment has been vast. Inexact alignments can take up to 90% of total CPU time in bioinformatics pipelines. High-performance Integrated Virtual Environment (HIVE), a cloud-based environment optimized for storage and analysis of extra-large data, presents an algorithmic solution: the HIVE-hexagon DNA sequence aligner.

A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages.

The rat has been used extensively as a model for evaluating chemical toxicities and for understanding drug mechanisms. However, its transcriptome across multiple organs, or developmental stages, has not yet been reported. Here we show, as part of the SEQC consortium efforts, a comprehensive rat transcriptomic BodyMap created by performing RNA-Seq on 320 samples from 11 organs of both sexes of juvenile, adolescent, adult and aged Fischer 344 rats.