Biology subjects

Mukherjee, B.

Publications and source records attributed to Mukherjee, B..

4 recordsLinked to original sources

bioRxiv2018

Proprioceptive Sonomyographic Control: A novel method of intuitive proportional control of multiple degrees of freedom for upper-extremity amputees

Technological advances in multi-articulated prosthetic hands have outpaced the methods available to amputees to intuitively control these devices. Amputees often cite difficulty of use as a key contributing factor for abandoning their prosthesis, creating a pressing need for improved control technology. A major challenge of traditional myoelectric control strategies using surface electromyography electrodes has been the difficulty in achieving intuitive and robust proportional control of multiple degrees of freedom. In this paper, we describe a new control method, proprioceptive sonomyographic control that overcomes several limitations of myoelectric control. In sonomyography, muscle mechanical deformation is sensed using ultrasound, as compared to electrical activation, and therefore the resulting control signals can directly control the position of the end effector. Compared to myoelectric control which controls the velocity of the end-effector device, sonomyographic control is more congruent with residual proprioception in the residual limb. We tested our approach with 5 upper-extremity amputees and able-bodied subjects using a virtual target achievement and holding task. Amputees and able-bodied participants demonstrated the ability to achieve positional control for 5 degrees of freedom with an hour of training. Our results demonstrate the potential of proprioceptive sonomyographic control for intuitive dexterous control of multiarticulated prostheses.

bioengineering↗

bioRxiv2018

Exploring Various Polygenic Risk Scores for Basal Cell Carcinoma, Cutaneous Squamous Cell Carcinoma and Melanoma in the Phenomes of the Michigan Genomics Initiative and the UK Biobank

Polygenic risk scores (PRS) are designed to serve as a single summary measure, condensing information from a large number of genetic variants associated with a disease. They have been used for stratification and prediction of disease risk. The construction of a PRS often depends on the purpose of the study, the available data/summary estimates, and the underlying genetic architecture of a disease. In this paper, we consider several choices for constructing a PRS using summary data obtained from various publicly-available sources including the UK Biobank and evaluate their abilities to predict outcomes derived from electronic health records (EHR). Weexamine the three most common skin cancer subtypes in the USA: basal cellcarcinoma, cutaneous squamous cell carcinoma, and melanoma. The genetic risk profiles of subtypes may consist of both shared and unique elements and we construct PRS to understand the common versus distinct etiology. This study is conducted using data from 30,702 unrelated, genotyped patients of recent European descent from the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort within Michigan Medicine. Using these PRS for various skin cancer subtypes, we conduct a phenome-wide association study (PheWAS) within the MGI data to evaluate their association with secondary traits. PheWAS results are then replicated using population-based UK Biobank data. We develop an accompanying visual catalog called PRSweb that provides detailed PheWAS results and allows users to directly compare different PRS construction methods. The results of this study can provide guidance regarding PRS construction in future PRS-PheWAS studies using EHR data involving disease subtypes.\n\nAuthor summaryIn the study of genetically complex diseases, polygenic risk scores synthesize information from multiple genetic risk factors to provide insight into a patients risk of developing a disease based on his/her genetic profile. These risk scores can be explored in conjunction with health and disease information available in the electronic medical records. They may be associated with diseases that may be related to or precursors of the underlying disease of interest. Limited work is available guiding risk score construction when the goal is to identify associations across the medical phenome. In this paper, we compare different polygenic risk score construction methods in terms of their relationships with the medical phenome. We further propose methods for using these risk scores to decouple the shared and unique genetic profiles of related diseases and to explore related diseases shared and unique secondary associations. Leveraging and harnessing the rich data resources of the Michigan Genomics Initiative, a biorepository effort at Michigan Medicine, and the larger population-based UK Biobank study, we investigated the performance of genetic risk profiling methods for the three most common types of skin cancer: melanoma, basal cell carcinoma and squamous cell carcinoma.

genetics↗

bioRxiv2018

Subset-Based Analysis using Gene-Environment Interactions for Discovery of Genetic Associations across Multiple Studies or Phenotypes

ObjectivesClassical methods for combining summary data from genome-wide association studies (GWAS) only use marginal genetic effects and power can be compromised in the presence of heterogeneity. We aim to enhance the discovery of novel associated loci in the presence of heterogeneity of genetic effects in sub-groups defined by an environmental factor.\n\nMethodsWe present a p-value Assisted Subset Testing for Associations (pASTA) framework that generalizes the previously proposed association analysis based on subsets (ASSET) method by incorporating gene-environment (G-E) interactions into the testing procedure. We conduct simulation studies and provide two data examples.\n\nResultsSimulation studies show that our proposal is more powerful than methods based on marginal associations in the presence of G-E interactions and maintains comparable power even in their absence. Both data examples demonstrate that our method can increase power to detect overall genetic associations and identify novel studies/phenotypes that contribute to the association.\n\nConclusionsOur proposed method can be a useful screening tool to identify candidate single nucleotide polymorphisms (SNPs) that are potentially associated with the trait(s) of interest for further validation. It also allows researchers to determine the most probable subset of traits that exhibit genetic associations in addition to the enhancement of power.

genetics↗

bioRxiv2017

Association of Polygenic Risk Scores for Multiple Cancers in a Phenome-wide Study: Results from The Michigan Genomics Initiative

Health systems are stewards of patient electronic health record (EHR) data with extraordinarily rich depth and breadth, reflecting thousands of diagnoses and exposures. Measures of genomic variation integrated with EHRs offer a potential strategy to accurately stratify patients for risk profiling and discover new relationships between diagnoses and genomes. The objective of this study was to evaluate whether Polygenic Risk Scores (PRS) for common cancers are associated with multiple phenotypes in a Phenome-wide Association Study (PheWAS) conducted in 28,260 unrelated, genotyped patients of recent European ancestry who consented to participate in the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine. PRS for 12 cancer traits were calculated using summary statistics from the NHGRI-EBI catalog. A total of 1,711 synthetic case-control studies was used for PheWAS analyses. There were 13,490 (47.7%) patients with at least one cancer diagnosis in this study sample. PRSs exhibited strong association for several cancer traits they were designed for including female breast cancer, prostate cancer, melanoma, basal cell carcinoma, squamous cell carcinoma and thyroid cancer. Phenome-wide significant associations were observed between PRS and many non-cancer diagnoses. To differentiate PRS associations driven by the primary trait from associations arising through shared genetic risk profiles, the idea of \"exclusion PRS PheWAS\" was introduced. This approach led to phenome-wide significant associations between a lower risk for hypothyroidism in patients with high thyroid cancer PRS and a higher risk for actinic keratosis in patients with high squamous cell carcinoma PRS after removing all cases of the primary cancer trait. Further analysis of temporal order of the diagnoses improved our understanding of these secondary associations. This is the first comprehensive PheWAS study using PRS instead of a single variant.

genetics↗