Genotype concordance and polygenic risk score estimation across consumer genetic testing data.

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services-two single nucleotide polymorphism (SNP)-array based and one sequencing based.

Hair Loss in Lichen Planopilaris and Frontal Fibrosing Alopecia: Not Always Irreversible.

Introduction: We present 2 cases in which typically irreversible lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) showed signs of reversal.

Case Presentation: A 27-year-old Caucasian man presented with hair loss and intense pruritus on the vertex scalp for 4 years with biopsy-proven LPP and having failed multiple pharmacologic modalities. Six months after adding oral tofacitinib and later dapsone, he demonstrated reduced scalp visibility, evidence of crown and vertex hair regrowth, and elimination of itch.

Quantitative lung morphology: semi-automated measurement of mean linear intercept.

Background: Quantifying morphologic changes is critical to our understanding of the pathophysiology of the lung. Mean linear intercept (MLI) measures are important in the assessment of clinically relevant pathology, such as emphysema. However, qualitative measures are prone to error and bias, while quantitative methods such as mean linear intercept (MLI) are manually time consuming.

Database of evidence for precision oncology portal.

Summary: A database of curated genomic variants with clinically supported drug therapies and other oncological annotations is described. The accompanying web portal provides a search engine with two modes: one that allows users to query gene, cancer type, variant type or position for druggable mutations, and another to search for and to visualize, on three-dimensional protein structures, putative druggable sites that cluster with known druggable mutations.

Availability And Implementation: http://dinglab.

Genomic Stability in Syndromic Basal Cell Carcinoma.

Basal cell cancers (BCCs) are characterized by upregulation of Hedgehog pathway through loss of PTCH1 or activation of SMO, and SMO inhibitors, such as vismodegib, are effective therapies for advanced BCCs. Although most BCCs are sporadic, rare individuals with basal cell nevus syndrome (BCNS) harbor germline defects in PTCH1 and develop up to hundreds of tumors that are histopathologically indistinguishable from sporadic BCCs. Interestingly, BCNS-BCCs are more responsive to SMO inhibitors than sporadic BCCs, with minimal development of resistance.

Protein-structure-guided discovery of functional mutations across 19 cancer types.

Local concentrations of mutations are well known in human cancers. However, their three-dimensional spatial relationships in the encoded protein have yet to be systematically explored. We developed a computational tool, HotSpot3D, to identify such spatial hotspots (clusters) and to interpret the potential function of variants within them.

Resting state functional connectivity magnetic resonance imaging integrated with intraoperative neuronavigation for functional mapping after aborted awake craniotomy.

Background: Awake craniotomy is currently the gold standard for aggressive tumor resections in eloquent cortex. However, a significant subset of patients is unable to tolerate this procedure, particularly the very young or old or those with psychiatric comorbidities, cardiopulmonary comorbidities, or obesity, among other conditions. In these cases, typical alternative procedures include biopsy alone or subtotal resection, both of which are associated with diminished surgical outcomes.

Patterns and functional implications of rare germline variants across 12 cancer types.

Large-scale cancer sequencing data enable discovery of rare germline cancer susceptibility variants. Here we systematically analyse 4,034 cases from The Cancer Genome Atlas cancer cases representing 12 cancer types. We find that the frequency of rare germline truncations in 114 cancer-susceptibility-associated genes varies widely, from 4% (acute myeloid leukaemia (AML)) to 19% (ovarian cancer), with a notably high frequency of 11% in stomach cancer.

Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data.

High throughput sequencing has facilitated a precipitous drop in the cost of genomic sequencing, prompting predictions of a revolution in medicine via genetic personalization of diagnostic and therapeutic strategies. There are significant barriers to realizing this goal that are related to the difficult task of interpreting personal genetic variation. A comprehensive, widely accessible application for interpretation of whole genome sequence data is needed.