Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG).

There is a growing attention toward personalized medicine. This is led by a fundamental shift from the 'one size fits all' paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data "10 Vs" and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.

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Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics

The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom.

Charcot-Marie-Tooth disease and the related disorders hereditary motor neuropathy and hereditary sensory neuropathy, collectively termed CMT, are the commonest group of inherited neuromuscular diseases, and they exhibit wide phenotypic and genetic heterogeneity. CMT is usually characterized by distal muscle atrophy, often with foot deformity, weakness and sensory loss. In the past decade, next-generation sequencing (NGS) technologies have revolutionized genomic medicine and, as these technologies are being applied to clinical practice, they are changing our diagnostic approach to CMT. In this Review, we discuss the application of NGS technologies, including disease-specific gene panels, whole-exome sequencing, whole-genome sequencing (WGS), mitochondrial sequencing and high-throughput transcriptome sequencing, to the diagnosis of CMT. We discuss the growing challenge of variant interpretation and consider how the clinical phenotype can be combined with genetic, bioinformatic and functional evidence to assess the pathogenicity of genetic variants in patients with CMT. WGS has several advantages over the other techniques that we discuss, which include unparalleled coverage of coding, non-coding and intergenic areas of both nuclear and mitochondrial genomes, the ability to identify structural variants and the opportunity to perform genome-wide dense homozygosity mapping. We propose an algorithm for incorporating WGS into the CMT diagnostic pathway.

/pdf/next-generation-sequencing-in-charcot-marie-tooth-disease-24t0enkax9.pdf

Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges.

Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature.

Are whole Exome and whole Genome Sequencing Approaches Cost-Effective? A Systematic Review of the Literature

Patients with Parkinson's Disease (PD) require an all-encompassing and individualized care including pharmacological as well as non-pharmacological treatment approaches, such as physical therapy, occupational therapy and speech and swallowing therapy. ParkinsonAKTIV is an innovative, multidisciplinary, and comprehensive approach to guide this non-pharmacological PD treatment in northwestern Germany. Its online communication platform called JamesAKTIV has been developed to enhance and standardize PD healthcare professionals' communication. The implementation of ParkinsonAKTIV and JamesAKTIV is accompanied through a detailed process evaluation and to gather evidence on the impact on patient-related outcomes, such as health-related quality of life and healthcare costs for people with PD through an effectiveness evaluation.The study design contains two parts: (1) first, a quantitative effectiveness evaluation is conducted utilizing a prospective quasi-experimental approach with a control group which examines PD patient's health-related quality of life and physician-assessed PD patient's health status (Unified Parkinson Disease Rating Scale). Moreover, a health economic evaluation of the ParkinsonAKTIV intervention is conducted using patient-reported outcomes and cost data as well as routine data from a statutory health insurance. (2) Second, a mixed-methods process evaluation among healthcare professionals, which examines the feasibility and potential barriers and facilitators of ParkinsonAKTIV for routine care, is performed. Quantitative results from a social network analysis and a survey among healthcare professionals will be triangulated with data from qualitative stakeholder interviews and focus group discussions.Findings are expected to provide evidence of an increase in quality of life of patients with PD, less severe PD symptoms, and a better ability to participate in activities of daily living. ParkinsonAKTIV has the potential of increasing PD patients' quality of care through sufficient and more tailored prescription of non-pharmacological therapies. It is anticipated that ParkinsonAKTIV will improve communication among health professionals. Results from the ParkinsonAKTIV study will provide first practice-oriented evidence and a roadmap for implementation of an online tool for a comprehensive, multidisciplinary care PD network for patients and their caregivers in routine care in Germany. Trial registration ClinicalTrials.gov: registration number NCT05251298 (retrospectively registered: https://clinicaltrials.gov/ct2/show/record/NCT05251298 ). 

/pdf/design-and-implementation-of-parkinsonaktiv-an-2mezbexf.pdf

Design and implementation of ParkinsonAKTIV: an interventional study to evaluate the effectiveness of a novel online platform to guide quickcard-based treatment decisions

Katharina Schwarze

Papers

Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature.

The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom.

Are whole Exome and whole Genome Sequencing Approaches Cost-Effective? A Systematic Review of the Literature

Design and implementation of ParkinsonAKTIV: an interventional study to evaluate the effectiveness of a novel online platform to guide quickcard-based treatment decisions