The complete sequence of a human genome

In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.

Immunoinformatics Patterns and Characteristic of Epitope-Based Peptide Vaccine candidates against COVID-19

Vaccination as defined by the WHO is “the administration of agent-specific, but safe, antigenic components that in vaccinated individuals can induce protective immunity against the corresponding infectious agent”. Regardless of their debated history, the standard vaccine approaches have been unsuccessful in providing vaccines for numerous infectious organisms. In the recent three decades, an enormous amount of immunological data was retrieved from clinical studies due to the advancement in human genome sequencing. These data are being deposited in databases and numerous scientific literature. The development of several bioinformatics tools to analyze this rapidly increasing immunological databank has given rise to the field of immunoinformatics. This approach allows the selection of immunogenic residues from the pathogen genomes. The ideal residues could be industrialized as vaccine candidates to provide protective immune responses in the hosts. This methodology will significantly decrease the time and cost needed for the vaccine development. This review focus on published articles that proposed as vaccine candidates through immunoinformatics analysis. The reviewed Published immunoinformatics studies provided vaccine peptide candidates against SARS-COV-2, which is based on functional and non functional immunogenic proteins like open reading frame , spike protein, envelope protein and membranous protein .All of which are designed by unique strategies like reverse vaccinology . Spike protein was the most common used target with different suggeststed B and T cell peptides due to the difference in methodology between the findings.

The Computational Patient has Diabetes and a COVID

Medicine is moving from reacting to a disease to prepare personalised and precision paths to well being. The complex and multi level pathophysiological patterns of most diseases require a systemic medicine approach and are challenging current medical therapies. Computational medicine is a vibrant interdisciplinary field that could help moving from an organ-centered to a process-oriented or systemic medicine data analysis. The resulting Computational patient may require an international interdisciplinary effort, probably of larger scientific and technological interdisciplinarity than the human genome sequencing. When deployed, it will have a profound impact on how healthcare is delivered to patients. Here we present a Computational patient model that integrates, refine and extend recent specific mechanistic or phenomenological models of cardiovascular, RAS and diabetic processes. Our aim is twofold: analyse the modularity and composability of the models-building blocks of the Computational patient and to study the dynamical properties of well-being and disease states in a broader functional context. We present results from a number of experiments among which we characterise the dynamical impact of covid-19 and T2D diabetes on cardiovascular and inflammation conditions. We tested these experiments under exercise and meals and drug regimen. We report results showing the striking importance of transient dynamical responses to acute state conditions and we provide guidelines for system design principle of the inter-relationship between modules and components for systemic medicine. Finally this initial Computational Patient can be used as a toolbox for further modifications and extensions.

Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico’s Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations.

Variant calling and quality control of large-scale human genome sequencing data

Next-generation sequencing has allowed genetic studies to collect genome sequencing data from a large number of individuals. However, raw sequencing data are not usually interpretable due to fragmentation of the genome and technical biases; therefore, analysis of these data requires many computational approaches. First, for each sequenced individual, sequencing data are aligned and further processed to account for technical biases. Then, variant calling is performed to obtain information on the positions of genetic variants and their corresponding genotypes. Quality control (QC) is applied to identify individuals and genetic variants with sequencing errors. These procedures are necessary to generate accurate variant calls from sequencing data, and many computational approaches have been developed for these tasks. This review will focus on current widely used approaches for variant calling and QC.

ARBoR: an identity and security solution for clinical reporting

Motivation Clinical genome sequencing laboratories return reports containing clinical testing results, signed by a board-certified clinical geneticist, to the ordering physician. This report is often a PDF, but can also be a paper copy or a structured data file. The reports are frequently modified and reissued due to changes in variant interpretation or clinical attributes. Materials and Methods To precisely track report authenticity, we developed ARBoR (Authenticated Resources in a Hashed Block Registry), an application for tracking the authenticity and lineage of versioned clinical reports even when they are distributed as PDF or paper copies. ARBoR tracks clinical reports as cryptographically signed hash blocks in an electronic ledger file, which is then exactly replicated to many clients. Results ARBoR was implemented for clinical reporting in the Human Genome Sequencing Center Clinical Laboratory, initially as part of the National Institute of Health's Electronic Medical Record and Genomics (eMERGE) project. Conclusions To date, we have issued 15 205 versioned clinical reports tracked by ARBoR. This system has provided us with a simple and tamper-proof mechanism for tracking clinical reports with a complicated update history.