SAM-dPCR: Accurate and Generalist Nuclei Acid Quantification Leveraging the Zero-Shot Segment Anything Model.

Digital PCR (dPCR) has transformed nucleic acid diagnostics by enabling the absolute quantification of rare mutations and target sequences. However, traditional dPCR detection methods, such as those involving flow cytometry and fluorescence imaging, may face challenges due to high costs, complexity, limited accuracy, and slow processing speeds. In this study, SAM-dPCR is introduced, a training-free open-source bioanalysis paradigm that offers swift and precise absolute quantification of biological samples.

Chemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells.

Definitive endoderm (DE) derived from human pluripotent stem cells (hPSCs) holds great promise for cell-based therapies and drug discovery. However, current DE differentiation methods required undefined components and/or expensive recombinant proteins, limiting their scalable manufacture and clinical use. Homogeneous DE differentiation in defined and recombinant protein-free conditions remains a major challenge.

Characterization of cancer-driving nucleotides (CDNs) across genes, cancer types, and patients.

A central goal of cancer genomics is to identify, in each patient, all the cancer-driving mutations. Among them, point mutations are referred to as cancer-driving nucleotides (CDNs), which recur in cancers. The companion study shows that the probability of recurrent hits in patients would decrease exponentially with ; hence, any mutation with ≥ 3 hits in The Cancer Genome Atlas (TCGA) database is a high-probability CDN.

STRsensor: a computationally efficient method for STR allele-typing from massively parallel sequencing data.

Short tandem repeats (STRs) represent one of the most polymorphic variations in the human genome, finding extensive applications in forensics, population genetics and medical genetics. In contrast to the traditional capillary electrophoresis (CE) method, genotyping STRs using massive parallel sequencing technology offers enhanced sensitivity and accuracy. However, current methods are mainly designed for target sequencing with higher coverage for a specific STR locus, thereby constraining the utility of STRs in low- and medium-coverage whole genome sequencing (WGS) data.

Hydrogel bead-based isothermal detection (BEAD-ID) for assessing the activity of DNA-modifying enzymes.

DNA-modifying enzymes are crucial in biological processes and have significant clinical implications. Traditional quantification methods often overlook enzymatic activity, the true determinants of enzymes' functions. We present hydrogel Bead-based Isothermal Detection (BEAD-ID), utilizing uniform hydrogel bead-based microreactors to evaluate DNA-modifying enzyme activity on-bead.

A methylation panel of 10 CpGs for accurate age inference via stepwise conditional epigenome-wide association study.

Estimating individual age from DNA methylation at age associated CpG sites may provide key information facilitating forensic investigations. Systematic marker screening and feature selection play a critical role in ensuring the performance of the final prediction model. In the discovery stage, we screened for 811876 CpGs from whole blood of 2664 Chinese individuals ranging from 18 to 83 years of age based on a stepwise conditional epigenome-wide association study (SCEWAS).

Single-nucleus multi-omics analyses reveal cellular and molecular innovations in the anterior cingulate cortex during primate evolution.

The anterior cingulate cortex (ACC) of the human brain is involved in higher-level cognitive functions such as emotion and self-awareness. We generated profiles of human and macaque ACC gene expression and chromatin accessibility at single-nucleus resolution. We characterized the conserved patterns of gene expression, chromatin accessibility, and transcription factor binding in different cell types.

The E3 ubiquitin ligase RNF220 maintains hindbrain expression patterns through regulation of WDR5 stability.

The spatial and temporal linear expression of genes establishes a regional code, which is crucial for the antero-posterior (A-P) patterning, segmentation, and neuronal circuit development of the hindbrain. RNF220, an E3 ubiquitin ligase, is widely involved in neural development via targeting of multiple substrates. Here, we found that the expression of genes in the pons was markedly up-regulated at the late developmental stage (post-embryonic day E15.

Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans.

Adaptation to high-altitude hypoxia is characterized by systemic and organ-specific metabolic changes. This study investigates whether intestinal metabolic rewiring is a contributing factor to hypoxia adaptation. We conducted a longitudinal analysis over 108 days, with seven time points, examining fecal metabolomic data from a cohort of 46 healthy male adults traveling from Chongqing (a.

Repressor elements provide insights into tissue development and phenotypes in pigs.

Repressor elements significantly influence economically relevant phenotypes in pigs; however, their precise roles and characteristics are inadequately understood. In the present study, we employed H3K27me3 profiling, assay for transposase-accessible chromatin with highthroughput sequencing (ATAC-seq), and RNA sequencing (RNA-seq) data across six tissues derived from three embryonic layers to identify and map 2 034 super repressor elements (SREs) and 22 223 typical repressor elements (TREs) in the pig genome. Notably, many repressor elements were conserved across mesodermal and ectodermal tissues.

SMART: STR Mixture Analysis and Resolution Tools.

The analysis of STR mixture profiles derived from mixed DNA samples plays a critical role in criminal investigations and legal proceedings. In this article, we present SMART, a novel software developed within the fully continuous model framework to analyze STR mixture profiles. SMART incorporates the peak height model, stutter model, drop-in/drop-out model, and population genetics model, offering various functionalities such as calculating likelihood ratios (LR), resolving genotypes of individual contributors, and performing direct database searches using mixed DNA profiles.

Identifications of the potential in-silico biomarkers in lung cancer tissue microbiomes.

It is postulated that the tumor tissue microbiome is one of the enabling characteristics that can either promote or suppress the ability of tumors to acquire certain hallmarks of cancer. This underscores its critical importance in carcinogenesis, cancer progression, and therapy responses. However, characterizing the tumor microbiomes is extremely challenging because of their low biomass and severe difficulties in controlling laboratory-borne contaminants, which is further aggravated by lack of comprehensively effective computational approaches to identify unique or enriched microbial species associated with cancers.

Metabolic regulation of mitochondrial morphologies in pancreatic beta cells: coupling of bioenergetics and mitochondrial dynamics.

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells.

Longitudinal association of peripheral blood DNA methylation with liver fat content: distinguishing between predictors and biomarkers.

Background: Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, and explore their temporal relationships.

Methods: Data were obtained from 2 waves over a four-year time period of the Shanghai Changfeng Study (discovery, n = 407 and replication, n = 126).

HaploSweep: Detecting and Distinguishing Recent Soft and Hard Selective Sweeps through Haplotype Structure.

Identifying soft selective sweeps using genomic data is a challenging yet crucial task in population genetics. In this study, we present HaploSweep, a novel method for detecting and categorizing soft and hard selective sweeps based on haplotype structure. Through simulations spanning a broad range of selection intensities, softness levels, and demographic histories, we demonstrate that HaploSweep outperforms iHS, nSL, and H12 in detecting soft sweeps.

An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.

Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations.