Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features.

Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene.

Racial and Ethnic Disparities in Food Insufficiency in Families with Children During the COVID-19 Pandemic: the Role of Risk and Protective Factors.

Background: Black and Hispanic households are at elevated risk of food insecurity and insufficiency-correlates of adverse outcomes in areas such as health and mental health-relative to White households in the USA. The COVID-19 pandemic and its economic shock threatened to further exacerbate these issues. Research has identified a number of risk and protective factors for food insecurity and insufficiency.

Heterozygous loss-of-function variants are associated with variable and incompletely penetrant growth and developmental features.

Heterozygous missense variants and in-frame indels in are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in , and analyzed population databases to characterize mutational intolerance in this gene.

Using a chat-based informed consent tool in large-scale genomic research.

Objective: We implemented a chatbot consent tool to shift the time burden from study staff in support of a national genomics research study.

Materials And Methods: We created an Institutional Review Board-approved script for automated chat-based consent. We compared data from prospective participants who used the tool or had traditional consent conversations with study staff.

"Development and Implementation of Novel Chatbot-based Genomic Research Consent".

Objective: To conduct a retrospective analysis comparing traditional human-based consenting to an automated chat-based consenting process.

Materials And Methods: We developed a new chat-based consent using our IRB-approved consent forms. We leveraged a previously developed platform (Gia, or "Genetic Information Assistant") to deliver the chat content to candidate participants.

State Variation in TANF Expenditures: Implications for Social Work and Social Policy.

The Temporary Assistance for Needy Families (TANF) program is a federal block grant to the states, with a required state contribution. Although often viewed as a cash assistance program with work requirements and services targeted at extremely low-income families with children, only about one-quarter of all state and federal TANF funds are now used for traditional cash aid. Uses of funds vary widely by state, and alternatives range from refundable tax credits to support of state child welfare systems.

Trans-ethnic variation in germline variants of patients with renal cell carcinoma.

Prior studies of the renal cell carcinoma (RCC) germline landscape investigated predominantly patients of European ancestry. We examine the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 1,829 patients with RCC from various ancestries. Overall, P/LP variants are found in 17% of patients, among whom 10.

Food insecurity among women of reproductive age in Nepal: prevalence and correlates.

Background: Food insecurity is widely prevalent in certain sections of society in low and middle-income countries. The United Nations has challenged all member countries to eliminate hunger for all people by 2030. This study examines the prevalence and correlates of household food insecurity among women, especially Dalit women of reproductive age in Nepal.

Racial and Ethnic Disparities in the Lifetime Prevalence of Homelessness in the United States.

Homelessness in the United States is often examined using cross-sectional, point-in-time samples. Any experience of homelessness is a risk factor for adverse outcomes, so it is also useful to understand the incidence of homelessness over longer periods. We estimate the lifetime prevalence of homelessness among members of the Baby Boom cohort (n = 6,545) using the 2012 and 2014 waves of the Health and Retirement Study (HRS), a nationally representative survey of older Americans.

Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration - experience from a pediatric tertiary care facility.

Objective: This paper outlines the implementation of a comprehensive clinical pharmacogenomics (PGx) service within a pediatric teaching hospital and the integration of clinical decision support in the electronic health record (EHR).

Materials And Methods: An approach to clinical decision support for medication ordering and dispensing driven by documented PGx variant status in an EHR is described. A web-based platform was created to automatically generate a clinical report from either raw assay results or specified diplotypes, able to parse and combine haplotypes into an interpretation for each individual and compared to the reference lab call for accuracy.

A Python package for parsing, validating, mapping and formatting sequence variants using HGVS nomenclature.

Unlabelled: Biological sequence variants are commonly represented in scientific literature, clinical reports and databases of variation using the mutation nomenclature guidelines endorsed by the Human Genome Variation Society (HGVS). Despite the widespread use of the standard, no freely available and comprehensive programming libraries are available. Here we report an open-source and easy-to-use Python library that facilitates the parsing, manipulation, formatting and validation of variants according to the HGVS specification.

The potential of accelerating early detection of autism through content analysis of YouTube videos.

Autism is on the rise, with 1 in 88 children receiving a diagnosis in the United States, yet the process for diagnosis remains cumbersome and time consuming. Research has shown that home videos of children can help increase the accuracy of diagnosis. However the use of videos in the diagnostic process is uncommon.

Development of a scalable pharmacogenomic clinical decision support service.

Advances in sequencing technology are making genomic data more accessible within the healthcare environment. Published pharmacogenetic guidelines attempt to provide a clinical context for specific genomic variants; however, the actual implementation to convert genomic data into a clinical report integrated within an electronic medical record system is a major challenge for any hospital. We created a two-part solution that integrates with the medical record system and converts genetic variant results into an interpreted clinical report based on published guidelines.

Early detection of poor adherers to statins: applying individualized surveillance to pay for performance.

Background: Medication nonadherence costs $300 billion annually in the US. Medicare Advantage plans have a financial incentive to increase medication adherence among members because the Centers for Medicare and Medicaid Services (CMS) now awards substantive bonus payments to such plans, based in part on population adherence to chronic medications. We sought to build an individualized surveillance model that detects early which beneficiaries will fall below the CMS adherence threshold.

A systems approach to designing effective clinical trials using simulations.

Background: Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit in comparison with standard clinical therapy. This study demonstrates a computational framework to systematically evaluate preclinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes.

Methods And Results: We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs.

A simulation platform to examine heterogeneity influence on treatment.

Although a protocol aims to guide treatment management and optimize overall outcomes, the benefits and harms for each individual vary due to heterogeneity. Some protocols integrate clinical and genetic variation to provide treatment recommendation; it is not clear whether such integration is sufficient. If not, treatment outcomes may be sub-optimal for certain patient sub-populations.

Biomedical cloud computing with Amazon Web Services.

In this overview to biomedical computing in the cloud, we discussed two primary ways to use the cloud (a single instance or cluster), provided a detailed example using NGS mapping, and highlighted the associated costs. While many users new to the cloud may assume that entry is as straightforward as uploading an application and selecting an instance type and storage options, we illustrated that there is substantial up-front effort required before an application can make full use of the cloud's vast resources. Our intention was to provide a set of best practices and to illustrate how those apply to a typical application pipeline for biomedical informatics, but also general enough for extrapolation to other types of computational problems.

Cost-effective cloud computing: a case study using the comparative genomics tool, roundup.

Background: Comparative genomics resources, such as ortholog detection tools and repositories are rapidly increasing in scale and complexity. Cloud computing is an emerging technological paradigm that enables researchers to dynamically build a dedicated virtual cluster and may represent a valuable alternative for large computational tools in bioinformatics. In the present manuscript, we optimize the computation of a large-scale comparative genomics resource-Roundup-using cloud computing, describe the proper operating principles required to achieve computational efficiency on the cloud, and detail important procedures for improving cost-effectiveness to ensure maximal computation at minimal costs.

Genotator: a disease-agnostic tool for genetic annotation of disease.

Background: Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone.

Immunoaffinity enrichment and liquid chromatography-selected reaction monitoring mass spectrometry for quantitation of carbonic anhydrase 12 in cultured renal carcinoma cells.

Liquid chromatography-selected reaction monitoring (LC-SRM) is a highly specific and sensitive mass spectrometry (MS) technique that is widely being applied to selectively qualify and validate candidate markers within complex biological samples. However, in order for LC-SRM methods to take on these attributes, target-specific optimization of sample processing is required, in order to reduce analyte complexity, prior to LC-SRM. In this study, we have developed a targeted platform consisting of protein immunoaffinity enrichment on magnetic beads and LC-SRM for measuring carbonic anhydrase 12 (CA12) protein in a renal cell carcinoma (RCC) cell line (PRC3), a candidate biomarker for RCC whose expression at the protein level has not been previously reported.

Cloud computing for comparative genomics.

Background: Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward.

Prediction of high-responding peptides for targeted protein assays by mass spectrometry.

Protein biomarker discovery produces lengthy lists of candidates that must subsequently be verified in blood or other accessible biofluids. Use of targeted mass spectrometry (MS) to verify disease- or therapy-related changes in protein levels requires the selection of peptides that are quantifiable surrogates for proteins of interest. Peptides that produce the highest ion-current response (high-responding peptides) are likely to provide the best detection sensitivity.

Many Microbe Microarrays Database: uniformly normalized Affymetrix compendia with structured experimental metadata.

Many Microbe Microarrays Database (M3D) is designed to facilitate the analysis and visualization of expression data in compendia compiled from multiple laboratories. M3D contains over a thousand Affymetrix microarrays for Escherichia coli, Saccharomyces cerevisiae and Shewanella oneidensis. The expression data is uniformly normalized to make the data generated by different laboratories and researchers more comparable.