Functional annotation of genes overlapping copy number variants in autistic patients: focus on axon pathfinding

We have used Gene Ontology (GO) and pathway analyses to uncover the common functions associated to the genes overlapping Copy Number Variants (CNVs) in autistic patients. Our source of data were four published studies [1-4]. We first applied a two-step enrichment strategy for autism-specific genes. We fished out from the four mentioned studies a list of 2928 genes overall overlapping 328 CNVs in patients and we first selected a sub-group of 2044 genes after excluding those ones that are also involved in CNVs reported in the Database of Genomic Variants (enrichment step 1). We then selected from the step 1-enriched list a sub-group of 514 genes each of which was found to be deleted or duplicated in at least two patients (enrichment step 2). The number of statistically significant processes and pathways identified by the Database for Annotation, Visualization and Integrated Discovery and Ingenuity Pathways Analysis softwares with the step 2-enriched list was significantly higher compared to the step 1-enriched list. In addition, statistically significant GO terms, biofunctions and pathways related to nervous system development and function were exclusively identified by the step 2-enriched list of genes. Interestingly, 21 genes were associated to axon growth and pathfinding. The latter genes and other ones associated to nervous system in this study represent a new set of autism candidate genes deserving further investigation. In summary, our results suggest that the autism's "connectivity genes" in some patients affect very early phases of neurodevelopment, i.e., earlier than synaptogenesis.     

Identification of a patient with intellectual disability and de novo 3.7 Mb deletion supports the existence of a novel microdeletion syndrome in 2p14–p15

Microdeletions spanning 2p14–p15 have recently been described in two patients with developmental and speech delay and intellectual disability but no congenital malformations or severe facial dysmorphism. We report a 4-year-old boy with a de novo 3.7 Mb long deletion encompassing the region deleted in the previous cases. The patient had clinical features partly consistent with the published cases including intellectual disability, absent speech, microcephaly, long face, bulbous nasal tip and thin upper lip, but his overall clinical picture was more severe compared to the published patients. The identification of this additional patient and a detailed analysis of deletions identified in various patient cohorts and in normal individuals support the existence of a new rare microdeletion syndrome in 2p14–p15. Its critical region is in the vicinity of but clearly separate from the minimal region deleted in the well established 2p15–p16.1 microdeletion syndrome. A thorough comparison of the deletions and phenotypes indicates that multiple genes located in this region may be involved in intellectual functioning, and that some patients may show composite and more complex phenotypes due to deletions spanning both critical regions.     

Review of Covid-19 vaccine clinical trials - A puzzle with missing pieces

A year after the initial outbreak of Covid-19 pandemic, several Phase III clinical trials investigating vaccine safety and efficacy have been published. These vaccine candidates were developed by different research groups and pharmaceutical companies with various vaccine technologies including mRNA, recombinant protein, adenoviral vector and inactivated virus-based platforms. Despite numerous successful clinical trials, participants enrolled in these trials are limited by trial inclusion and exclusion criteria, geographic location and viral outbreak situation. Many questions still remain, especially for specific subgroups, including the elderly, females with pregnancy and breastfeeding status, and adolescents. At the same time, vaccine efficacy towards asymptomatic infection and specific viral variants are still largely unknown. This review will cover vaccine candidates with Phase III clinical trial data released and discuss the scientific data available so far for these vaccine candidates for different subgroups of people and different viral variants.     

Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature

Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations. Although the diagnostic utility of clinical genetic testing in short stature has been implicated, the genetic architecture and the utility of genomic studies such as exome sequencing(ES) in a sizable cohort of patients with short stature have not been investigated systematically. In this study, we recruited 561 individuals with short stature from two centers in China during a 4-year period. We performed ES for all patients and available parents. All patients were retrospectively divided into two groups: an isolated short stature group(group I, n = 257) and an apparently syndromic short stature group(group II, n = 304). Causal variants were identified in 135 of 561(24.1%) patients. In group I, 29 of 257(11.3%) of the patients were solved by variants in 24 genes. In group II, 106 of 304(34.9%) patients were solved by variants in 57 genes. Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature. Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.     

Identification of indels in next-generation sequencing data

Background

The discovery and mapping of genomic variants is an essential step in most analysis done using sequencing reads. There are a number of mature software packages and associated pipelines that can identify single nucleotide polymorphisms (SNPs) with a high degree of concordance. However, the same cannot be said for tools that are used to identify the other types of variants. Indels represent the second most frequent class of variants in the human genome, after single nucleotide polymorphisms. The reliable detection of indels is still a challenging problem, especially for variants that are longer than a few bases.

Results

We have developed a set of algorithms and heuristics collectively called indelMINER to identify indels from whole genome resequencing datasets using paired-end reads. indelMINER uses a split-read approach to identify the precise breakpoints for indels of size less than a user specified threshold, and supplements that with a paired-end approach to identify larger variants that are frequently missed with the split-read approach. We use simulated and real datasets to show that an implementation of the algorithm performs favorably when compared to several existing tools.

Conclusions

indelMINER can be used effectively to identify indels in whole-genome resequencing projects. The output is provided in the VCF format along with additional information about the variant, including information about its presence or absence in another sample. The source code and documentation for indelMINER can be freely downloaded from www.bx.psu.edu/miller_lab/indelMINER.tar.gz.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0483-6) contains supplementary material, which is available to authorized users.     

The Impact of COVID-19 On Comorbidities: A Review Of Recent Updates For Combating It

Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.     

The significance of advanced COVID-19 diagnostic testing in pandemic control measures

During the 2 years since the start of the novel coronavirus disease 2019 (COVID-19) pandemic, the scientific world made an enormous effort to fight against this disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has high transmissibility. Advancements in vaccine and treatment strategies have reduced both the hospitalization and mortality rates. However, the virus has shown its ability to evolve and evade from our COVID-19 combating armamentaria by the most common evolution mechanism—mutation. Diagnostic testing has been the first line of defense following the identification of the causative agent. Ever since, the scientific community has developed nuclei acid-based, antigen-based, and antibody-based diagnostic tests, and these testing methodologies are still playing a central role in slowing down viral transmission. These testing methods have different sensitivity and specificity and could be optimally used in areas facing different challenges owing to different level and conditions of COVID-19 outbreak. In this review, we discuss these testing methodologies as well as the considerations on how to apply these diagnostic tests optimally in the community to cope with the ever-changing pandemic conditions.     

The induction of Staphylococcus aureus biofilm formation or Small Colony Variants is a strain-specific response to host-generated chemical stresses

Staphylococcus aureus is extremely versatile. It has a capacity to persist within its host by switching to the alternative lifestyles of biofilm or Small Colony Variants (SCV). The induction of this switch has been presumed to be in response to stressed conditions, however the environmental basis has not been thoroughly investigated. We assessed the response of numerous strains to chemicals that are present in human host. There were some that induced a biofilm or SCV phenotype and indeed some inducing both lifestyles. This result illustrates the diversity within a population and a strain-specific adaptation to the presence of host-generated stresses.