A statistical boosting framework for polygenic risk scores based on large-scale genotype data
Polygenic risk scores (PRS) evaluate the individual genetic liability to a certain trait and are expected to play an increasingly important role in clinical risk stratification. Most often, PRS are estimated based on summary statistics of univariate effects derived from genome-wide association studies. To improve the predictive performance of PRS, it is desirable to fit multivariable models directly on the genetic data. Due to the large and high-dimensional data, a direct application of existing methods is often not feasible and new efficient algorithms are required to overcome the computational burden regarding efficiency...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Novel immune-related prognostic model and nomogram for breast cancer based on ssGSEA
This study aimed to construct an immune-related prognostic model and a nomogram to predict the 1-, 3-, and 5-year overall survival (OS) of breast cancer patients. We applied single-sample gene set enrichment analysis to classify 1,053 breast cancer samples from The Cancer Genome Atlas (TCGA) database into high and low immune cell infiltration clusters. In cluster construction and validation, the R packages “GSVA,” “hclust,” “ESTIMATE,” and “CIBERSORT” and GSEA software were utilized. ImmPort, univariate Cox regression analysis, and Venn analysis were then used to identify 42 prognostic immune-related genes....
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Democratizing clinical-genomic data: How federated platforms can promote benefits sharing in genomics
Since the first sequencing of the human genome, associated sequencing costs have dramatically lowered, leading to an explosion of genomic data. This valuable data should in theory be of huge benefit to the global community, although unfortunately the benefits of these advances have not been widely distributed. Much of today’s clinical-genomic data is siloed and inaccessible in adherence with strict governance and privacy policies, with more than 97% of hospital data going unused, according to one reference. Despite these challenges, there are promising efforts to make clinical-genomic data accessible and useful without c...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

A novel 9-gene signature for the prediction of postoperative recurrence in stage II/III colorectal cancer
Conclusion: A novel RFS prediction model for patients with stage II/III CRC was constructed using multicohort validation. The proposed signature may help clinicians better manage patients with stage II/III CRC. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Epigenetic modifications in esophageal cancer: An evolving biomarker
Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modificati...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Case report: Infantile generalized pustular psoriasis with IL36RN and CARD14 gene mutations
Infantile pustular psoriasis (IPP) is an extremely rare skin disease associated with genetic factors. Gene mutations of IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment family member 14), and AP1S1 (the σ1C subunit of the adaptor protein complex 1) had been identified to be involved in the pathogenesis of IPP. IPP usually develops with no preceding psoriasis vulgaris (PV) or familial history. Here, we report a case of a 6-month-old infant and make the diagnosis of IPP by a series of examinations; subsequently, by detecting coexistent mutations of IL36RN and CARD14, the diagnosis is intensified from...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

A complex heterozygous mutation in PADI6 causes early embryo arrest: A case report
Conclusion: We found a complex heterozygous mutation in the PADI6 gene (c. 1247T>C; c. 2009_2010del) that caused embryos were arrested at the 1- or 2- cell stage. The discovery in this patient adds to the evidence showing the PADI6 gene mutation causes early embryo arrest in humans. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Transcriptomics and metabolomics reveal tolerance new mechanism of rice roots to Al stress
In this study, transcriptomics and metabolomics analyses were performed to reveal the mechanism of Al tolerance differences between two rice landraces (Al-tolerant genotype Shibanzhan (KR) and Al-sensitive genotype Hekedanuo (MR) with different Al tolerance. The results showed that DEG related to phenylpropanoid biosynthesis was highly enriched in KR and MR after Al stress, indicating that phenylpropanoid biosynthesis may be closely related to Al tolerance. E1.11.1.7 (peroxidase) was the most significant enzyme of phenylpropanoid biosynthesis in KR and MR under Al stress and is regulated by multiple genes. We further ident...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Editorial: Chromosomal fragile sites, genome instability and human diseases
(Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

A novel non-sense variant in the OFD1 gene caused Joubert syndrome
Conclusion: The genetic variation spectrum of JBS10 caused by OFD1 was broadened. The novel variants further deepened our insight into the molecular mechanism of the disease. (Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

The power of geohistorical boundaries for modeling the genetic background of human populations: The case of the rural catalan Pyrenees
In this study we have analyzed 726,718 autosomal single nucleotide variants in 435 individuals from the catalan Pyrenees covering around 200 km of a vast and abrupt region in the north of the Iberian Peninsula, for which we have information about the geographic origin of all grand-parents and parents. At a macro-geographic scale, our analyses recapitulate the genetic gradient observed in Spain. However, we also identified the presence of micro-population substructure among the sampled individuals. Such micro-population substructure does not correlate with geographic barriers such as the expected by the orography of the co...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer ’s disease
This study aimed to evaluate the role of CCT2 in Alzheimer’s disease. First, bioinformatics database analysis revealed that CCT2 was significantly downregulated in patients with Alzheimer’s disease and associated with autophagic clearance of β-amyloid. The 789 differentially expressed genes overlapped in AD-group and CCT2-low/high group, and the CCT2-high-associated genes screened by Pearson coefficients were enriched in protein folding, autophagy, and messenger RNA stability regulation pathways. These results suggest that CCT2 is significantly and positively associated with multiple pathways linked to autophagy and n...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Editorial: Application in evolutionary novelties and diversities: Medicine, agriculture, and conservation
(Source: Frontiers in Genetics)
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Whole-genome resequencing reveals genetic diversity, differentiation, and selection signatures of yak breeds/populations in Qinghai, China
The Qinghai Province of China is located in the northeast region of the Qinghai–Tibetan Plateau (QTP) and carries abundant yak genetic resources. Previous investigations of archaeological records, mitochondrial DNA, and Y chromosomal markers have suggested that Qinghai was the major center of yak domestication. In the present study, we examined the genomic diversity, differentiation, and selection signatures of 113 Qinghai yak, including 42 newly sequenced Qinghai yak and 71 publicly available individuals, from nine yak breeds/populations (wild, Datong, Huanhu, Xueduo, Yushu, Qilian, Geermu, Tongde, and Huzhu white) usin...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research

Revitalization of small millets for nutritional and food security by advanced genetics and genomics approaches
Small millets, also known as nutri-cereals, are smart foods that are expected to dominate food industries and diets to achieve nutritional security. Nutri-cereals are climate resilient and nutritious. Small millet-based foods are becoming popular in markets and are preferred for patients with celiac and diabetes. These crops once ruled as food and fodder but were pushed out of mainstream cultivation with shifts in dietary habits to staple crops during the green revolution. Nevertheless, small millets are rich in micronutrients and essential amino acids for regulatory activities. Hence, international and national organizati...
Source: Frontiers in Genetics - January 10, 2023 Category: Genetics & Stem Cells Source Type: research