The Translational Genomics Core at Partners Personalized Medicine: Facilitating the Transition of Research towards Personalized Medicine

The Translational Genomics Core (TGC) at Partners Personalized Medicine (PPM) serves as a fee-for-service core laboratory for Partners Healthcare researchers, providing access to technology platforms and analysis pipelines for genomic, transcriptomic, and epigenomic research projects. The interaction of the TGC with various components of PPM provides it with a unique infrastructure that allows for greater IT and bioinformatics opportunities, such as sample tracking and data analysis. The following article describes some of the unique opportunities available to an academic research core operating within PPM, such the ability to develop analysis pipelines with a dedicated bioinformatics team and maintain a flexible Laboratory Information Management System (LIMS) with the support of an internal IT team, as well as the operational challenges encountered to respond to emerging technologies, diverse investigator needs, and high staff turnover. In addition, the implementation and operational role of the TGC in the Partners Biobank genotyping project of over 25,000 samples is presented as an example of core activities working with other components of PPM

Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy

We sought to determine the mechanisms underlying failure of muscle regeneration that is observed in dystrophic muscle through hypothesis generation using muscle profiling data (human dystrophy and murine regeneration). We found that transforming growth factor β-centered networks strongly associated with pathological fibrosis and failed regeneration were also induced during normal regeneration but at distinct time points. We hypothesized that asynchronously regenerating microenvironments are an underlying driver of fibrosis and failed regeneration. We validated this hypothesis using an experimental model of focal asynchronous bouts of muscle regeneration in wild-type (WT) mice. A chronic inflammatory state and reduced mitochondrial oxidative capacity are observed in bouts separated by 4 d, whereas a chronic profibrotic state was seen in bouts separated by 10 d. Treatment of asynchronously remodeling WT muscle with either prednisone or VBP15 mitigated the molecular phenotype. Our asynchronous regeneration model for pathological fibrosis and muscle wasting in the muscular dystrophies is likely generalizable to tissue failure in chronic inflammatory states in other regenerative tissues

Meteorites on Mars observed with the Mars Exploration Rovers

Reduced weathering rates due to the lack of liquid water and significantly greater typical surface ages should result in a higher density of meteorites on the surface of Mars compared to Earth. Several meteorites were identified among the rocks investigated during Opportunity’s traverse across the sandy Meridiani plains. Heat Shield Rock is a IAB iron meteorite and has been officially recognized as ‘‘Meridiani Planum.’’ Barberton is olivine-rich and contains metallic Fe in the form of kamacite, suggesting a meteoritic origin. It is chemically most consistent with a mesosiderite silicate clast. Santa Catarina is a brecciated rock with a chemical and mineralogical composition similar to Barberton. Barberton, Santa Catarina, and cobbles adjacent to Santa Catarina may be part of a strewn field. Spirit observed two probable iron meteorites from its Winter Haven location in the Columbia Hills in Gusev Crater. Chondrites have not been identified to date, which may be a result of their lower strengths and probability to survive impact at current atmospheric pressures. Impact craters directly associated with Heat Shield Rock, Barberton, or Santa Catarina have not been observed, but such craters could have been erased by eolian-driven erosion.Additional co-authors: DW Ming, RV Morris, PA de Souza Jr, SW Squyres, C Weitz, AS Yen, J Zipfel, T Economo

Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission

Dissociating neural signatures of mental state retrodiction and classification based on facial expressions

Posed facial expressions of actors have often been used as stimuli to induce mental state inferences, in order to investigate “Theory of Mind” processes. However, such stimuli make it difficult to determine whether perceivers are using a basic or more elaborated mentalizing strategy. The current study used as stimuli covert recordings of target individuals who viewed various emotional expressions, which caused them to spontaneously mimic these expressions. Perceivers subsequently judged these subtle emotional expressions of the targets: In one condition (“classification”) participants were instructed to classify the target’s expression (i.e., match it to a sample) and in another condition (“retrodicting”) participants were instructed to retrodict (i.e., infer which emotional expression the target was viewing). When instructed to classify, participants showed more prevalent activations in event-related brain potentials (ERPs) at earlier and mid-latency ERP components N170, P200 and P300-600. By contrast, when instructed to retrodict participants showed enhanced late frontal and rontotemporal ERPs (N800-1000), with more sustained activity over the right than the left hemisphere. These findings reveal different cortical processes involved when retrodicting about a facial expression compared to merely classifying it, despite comparable performance on the behavioural tas

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions

The Translational Genomics Core at Partners Personalized Medicine: Facilitating the Transition of Research towards Personalized Medicine

The Translational Genomics Core (TGC) at Partners Personalized Medicine (PPM) serves as a fee-for-service core laboratory for Partners Healthcare researchers, providing access to technology platforms and analysis pipelines for genomic, transcriptomic, and epigenomic research projects. The interaction of the TGC with various components of PPM provides it with a unique infrastructure that allows for greater IT and bioinformatics opportunities, such as sample tracking and data analysis. The following article describes some of the unique opportunities available to an academic research core operating within PPM, such the ability to develop analysis pipelines with a dedicated bioinformatics team and maintain a flexible Laboratory Information Management System (LIMS) with the support of an internal IT team, as well as the operational challenges encountered to respond to emerging technologies, diverse investigator needs, and high staff turnover. In addition, the implementation and operational role of the TGC in the Partners Biobank genotyping project of over 25,000 samples is presented as an example of core activities working with other components of PPM

Toxoplasma secreting Cre recombinase for analysis of host-parasite interactions.

We describe a Toxoplasma gondii strain that will permit the use of site-specific recombination to study the host-parasite interactions of this organism. This Toxoplasma strain efficiently injects a Cre fusion protein into host cells. In a Cre-reporter cell line, a single parasite invasion induced Cre-mediated recombination in 95% of infected host cells. By infecting Cre-reporter mice with these parasites, we also monitored host-cell infection in vivo