Yves Lussier - Academia.edu (original) (raw)

Papers by Yves Lussier

American journal of respiratory and critical care medicine, 2014

Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 lino... more Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. To define a role for LYCAT in human and murine models of pulmonary fibrosis. We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two precl...

Convergent downstream candidate mechanisms of independent intergenic polymorphisms between co-cla... more Convergent downstream candidate mechanisms of independent intergenic polymorphisms between co-classified diseases implicate epistasis among noncoding elements. In PSB (pp. 524-535).

Figure S4. Reproducibility of comorbidity odds ratios observed in NIS13 (hospitalizations) and NE... more Figure S4. Reproducibility of comorbidity odds ratios observed in NIS13 (hospitalizations) and NEDS13 (emergency departments) HCUP datasets. The correlation R2 is 0.62 and 0.63 respectively. Top disease comorbidity was measured and compared directionally, and odds ratios are shown in a log scale. (DOCX 54 kb)

BMC Medical Genomics, Dec 1, 2018

Background: Forty-two percent of patients experience disease comorbidity, contributing substantia... more Background: Forty-two percent of patients experience disease comorbidity, contributing substantially to mortality rates and increased healthcare costs. Yet, the possibility of underlying shared mechanisms for diseases remains not well established, and few studies have confirmed their molecular predictions with clinical datasets. Methods: In this work, we integrated genome-wide association study (GWAS) associating diseases and single nucleotide polymorphisms (SNPs) with transcript regulatory activity from expression quantitative trait loci (eQTL). This allowed novel mechanistic insights for noncoding and intergenic regions. We then analyzed pairs of SNPs across diseases to identify shared molecular effectors robust to multiple test correction (False Discovery Rate FDR eRNA < 0.05). We hypothesized that disease pairs found to be molecularly convergent would also be significantly overrepresented among comorbidities in clinical datasets. To assess our hypothesis, we used clinical claims datasets from the Healthcare Cost and Utilization Project (HCUP) and calculated significant disease comorbidities (FDR comorbidity < 0.05). We finally verified if disease pairs resulting molecularly convergent were also statistically comorbid more than by chance using the Fisher's Exact Test. Results: Our approach integrates: (i) 6175 SNPs associated with 238 diseases from~1000 GWAS, (ii) eQTL associations from 19 tissues, and (iii) claims data for 35 million patients from HCUP. Logistic regression (controlled for age, gender, and race) identified comorbidities in HCUP, while enrichment analyses identified cis-and trans-eQTL downstream effectors of GWAS-identified variants. Among~16,000 combinations of diseases, 398 disease-pairs were prioritized by both convergent eQTL-genetics (RNA overlap enrichment, FDR eRNA < 0.05) and clinical comorbidities (OR > 1.5, FDR comorbidity < 0.05). Case studies of comorbidities illustrate specific convergent noncoding regulatory elements. An intergenic architecture of disease comorbidity was unveiled due to GWAS and eQTL-derived convergent mechanisms between distinct diseases being overrepresented among observed comorbidities in clinical datasets (OR = 8.6, p-value = 6.4 × 10 − 5 FET).

Cancer Research, Apr 1, 2012

Background: Cancer staging and treatment presumes a division into localized or metastatic disease... more Background: Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by β5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy. Methods: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy. Results: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression. Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3405. doi:1538-7445.AM2012-3405

PatientNarr summarizes information taken from textual discharge notes written by physicians, and ... more PatientNarr summarizes information taken from textual discharge notes written by physicians, and structured nursing documentation. It builds a graph that highlights the relationships between the two types of documentation; and extracts information from the graph for content planning. Sim-pleNLG is used for surface realization.

International Journal of Medical Informatics, May 1, 2018

Background-Physician and nurses have worked together for generations; however, their language and... more Background-Physician and nurses have worked together for generations; however, their language and training are vastly different; comparing and contrasting their work and their joint impact on patient outcomes is difficult in light of this difference. At the same time, the EHR only includes the physician perspective via the physician-authored discharge summary, but not nurse documentation. Prior research in this area has focused on collaboration and the usage of similar terminology.

Precision drug repurposing via convergent eQTL-based molecules and pathway targeting independent ... more Precision drug repurposing via convergent eQTL-based molecules and pathway targeting independent disease-associated polymorphisms. In PSB (pp. 308-319).

American Journal of Emergency Medicine, May 1, 2015

, the Center for Medicare and Medicaid Services will require medical providers to use the vastly ... more , the Center for Medicare and Medicaid Services will require medical providers to use the vastly expanded International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) system. Despite wide availability of information and mapping tools for the next generation of the ICD classification system, some of the challenges associated with transition from ICD-9-CM to ICD-10-CM are not well understood. To quantify the challenges faced by emergency physicians, we analyzed a subset of a 2010 Illinois Medicaid database of emergency department ICD-9-CM codes, seeking to determine the accuracy of existing mapping tools in order to better prepare emergency physicians for the change to the expanded ICD-10-CM system. We found that 27% of 1830 codes represented convoluted multidirectional mappings. We then analyzed the convoluted transitions and found that 8% of total visit encounters (23% of the convoluted transitions) were clinically incorrect. The ambiguity and inaccuracy of these mappings may impact the workflow associated with the translation process and affect the potential mapping between ICD codes and Current Procedural Codes, which determine physician reimbursement.

Single subject transcriptome analysis to identify functionally signed gene set or pathway activit... more Single subject transcriptome analysis to identify functionally signed gene set or pathway activity. In PSB (pp. 400-411).

Journal of the American Board of Family Medicine, 2016

The objective of this study was to examine the impact of the transition from International Classi... more The objective of this study was to examine the impact of the transition from International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), to Interactional Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), on family medicine and to identify areas where additional training might be required. Methods: Family medicine ICD-9-CM codes were obtained from an Illinois Medicaid data set (113,000 patient visits and $5.5 million in claims). Using the science of networks, we evaluated each ICD-9-CM code used by family medicine physicians to determine whether the transition was simple or convoluted. A simple transition is defined as 1 ICD-9-CM code mapping to 1 ICD-10-CM code, or 1 ICD-9-CM code mapping to multiple ICD-10-CM codes. A convoluted transition is where the transitions between coding systems is nonreciprocal and complex, with multiple codes for which definitions become intertwined. Three family medicine physicians evaluated the most frequently encountered complex mappings for clinical accuracy. Results: Of the 1635 diagnosis codes used by family medicine physicians, 70% of the codes were categorized as simple, 27% of codes were convoluted, and 3% had no mapping. For the visits, 75%, 24%, and 1% corresponded with simple, convoluted, and no mapping, respectively. Payment for submitted claims was similarly aligned. Of the frequently encountered convoluted codes, 3 diagnosis codes were clinically incorrect, but they represent only <0.1% of the overall diagnosis codes. Conclusions: The transition to ICD-10-CM is simple for 70% or more of diagnosis codes, visits, and reimbursement for a family medicine physician. However, some frequently used codes for disease management are convoluted and incorrect, and for which additional resources need to be invested to ensure a successful transition to ICD-10-CM.

Journal of Allergy and Clinical Immunology, 2022

BACKGROUND The study of pathogenic mechanisms in adult asthma is often marred by the lack of prec... more BACKGROUND The study of pathogenic mechanisms in adult asthma is often marred by the lack of precise information about the natural history of the disease. Children who have persistent wheezing during the first 6 years of life and whose symptoms start before age 3 (PW+) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma up to adult life than those who do not have persistent wheezing (PW-). OBJECTIVE To determine if nasal epithelial cells from PW+ adult asthmatics as compared with cells from PW- adult asthmatics show distinct biomechanistic processes activated by RV exposure. METHODS Air-liquid-interface (ALI) cultures derived from nasal epithelial cells of thirty 36-year old participants with active asthma with and without a history of persistent wheeze in childhood (PW+: n=10, PW-: n=20) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control and their RNA was sequenced. RESULTS 35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW+ from the PW- group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions, were invariably overactivated in PW+ patients and involved in toll-like receptor and cytokine-mediated responses, remodeling and angiogenic processes. CONCLUSIONS Adult asthmatics with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in responses to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.

Bioinformatics, 2015

Motivation: The conventional approach to personalized medicine relies on molecular data analytics... more Motivation: The conventional approach to personalized medicine relies on molecular data analytics across multiple patients. The path to precision medicine lies with molecular data analytics that can discover interpretable single-subject signals (N-of-1). We developed a global framework, N-of-1-pathways, for a mechanistic-anchored approach to single-subject gene expression data analysis. We previously employed a metric that could prioritize the statistical significance of a deregulated pathway in single subjects, however, it lacked in quantitative interpretability (e.g. the equivalent to a gene expression fold-change). Results: In this study, we extend our previous approach with the application of statistical Mahalanobis distance (MD) to quantify personal pathway-level deregulation. We demonstrate that this approach, N-of-1-pathways Paired Samples MD (N-OF-1-PATHWAYS-MD), detects deregulated pathways (empirical simulations), while not inflating false-positive rate using a study with ...

AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium, 2014

Earlier studies on hospitalization risk are largely based on regression models. To our knowledge,... more Earlier studies on hospitalization risk are largely based on regression models. To our knowledge, network modeling of multiple comorbidities is novel and inherently enables multidimensional scoring and unbiased feature reduction. Network modeling was conducted using an independent validation design starting from 38,695 patients, 1,446,581 visits, and 430 distinct clinical facilities/hospitals. Odds ratios (OR) were calculated for every pair of comorbidity using patient counts and compared their tendency with hospitalization rates and ED visits. Network topology analyses were performed, defining significant comorbidity associations as having OR≥5 & False-Discovery-Rate≤10(-7). Four COPD-associated comorbidity sub-networks emerged, incorporating multiple clinical systems: (i) metabolic syndrome, (ii) substance abuse and mental disorder, (iii) pregnancy-associated conditions, and (iv) fall-related injury. The latter two have not been reported yet. Features prioritized from the network ...

Genome biology, Jan 23, 2013

A report on the 21st Annual International Conference on Intelligent Systems for Molecular Biology... more A report on the 21st Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) and 12th European Conference on Computational Biology (ECCB), held in Berlin, Germany, July 21-23, 2013.

Journal of the American Medical Informatics Association : JAMIA, 2015

Reporting of hospital adverse events relies on Patient Safety Indicators (PSIs) using Internation... more Reporting of hospital adverse events relies on Patient Safety Indicators (PSIs) using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes. The US transition to ICD-10-CM in 2015 could result in erroneous comparisons of PSIs. Using the General Equivalent Mappings (GEMs), we compared the accuracy of ICD-9-CM coded PSIs against recommended ICD-10-CM codes from the Centers for Medicaid/Medicare Services (CMS). We further predict their impact in a cohort of 38,644 patients (1,446,581 visits and 399 hospitals). We compared the predicted results to the published PSI related ICD-10-CM diagnosis codes. We provide the first report of substantial hospital safety reporting errors with five direct comparisons from the 23 types of PSIs (transfusion and anesthesia related PSIs). One PSI was excluded from the comparison between code sets due to reorganization, while 15 additional PSIs were inaccurate to a lesser degree due to the complexity of the coding ...

Journal of the American Medical Informatics Association : JAMIA, Jan 12, 2015

In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, th... more In the United States, International Classification of Disease Clinical Modification (ICD-9-CM, the ninth revision) diagnosis codes are commonly used to identify patient cohorts and to conduct financial analyses related to disease. In October 2015, the healthcare system of the United States will transition to ICD-10-CM (the tenth revision) diagnosis codes. One challenge posed to clinical researchers and other analysts is conducting diagnosis-related queries across datasets containing both coding schemes. Further, healthcare administrators will manage growth, trends, and strategic planning with these dually-coded datasets. The majority of the ICD-9-CM to ICD-10-CM translations are complex and nonreciprocal, creating convoluted representations and meanings. Similarly, mapping back from ICD-10-CM to ICD-9-CM is equally complex, yet different from mapping forward, as relationships are likewise nonreciprocal. Indeed, 10 of the 21 top clinical categories are complex as 78% of their diagnos...

Journal of the American Medical Informatics Association : JAMIA

The emergence of precision medicine allowed the incorporation of individual molecular data into p... more The emergence of precision medicine allowed the incorporation of individual molecular data into patient care. Indeed, DNA sequencing predicts somatic mutations in individual patients. However, these genetic features overlook dynamic epigenetic and phenotypic response to therapy. Meanwhile, accurate personal transcriptome interpretation remains an unmet challenge. Further, N-of-1 (single-subject) efficacy trials are increasingly pursued, but are underpowered for molecular marker discovery. 'N-of-1-pathways' is a global framework relying on three principles: (i) the statistical universe is a single patient; (ii) significance is derived from geneset/biomodules powered by paired samples from the same patient; and (iii) similarity between genesets/biomodules assesses commonality and differences, within-study and cross-studies. Thus, patient gene-level profiles are transformed into deregulated pathways. From RNA-Seq of 55 lung adenocarcinoma patients, N-of-1-pathways predicts the ...

To improve patient engagement, EHR data needs to be organized and presented in a coherent summary... more To improve patient engagement, EHR data needs to be organized and presented in a coherent summary understandable to the patient. Focusing on inpatient hospital stays, we are developing a system combining physician discharge notes and nurse plans of care into a comprehensive narrative using patient accessible language.