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Mark P. Styczynski

Bio: Mark P. Styczynski is an academic researcher from Georgia Institute of Technology. The author has contributed to research in topics: Medicine & Metabolomics. The author has an hindex of 18, co-authored 66 publications receiving 1304 citations. Previous affiliations of Mark P. Styczynski include Massachusetts Institute of Technology & Yerkes National Primate Research Center.


Papers
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Journal ArticleDOI
TL;DR: This work presents a method and software implementation that can systematically detect components that are conserved across samples without the need for a reference library or manual curation, and demonstrates an application with a brief analysis of the Escherichia coli metabolome.
Abstract: Analysis of metabolomic profiling data from gas chromatography-mass spectrometry (GC/MS) measurements usually relies upon reference libraries of metabolite mass spectra to structurally identify and track metabolites. In general, techniques to enumerate and track unidentified metabolites are nonsystematic and require manual curation. We present a method and software implementation, freely available at http://spectconnect.mit.edu, that can systematically detect components that are conserved across samples without the need for a reference library or manual curation. We validate this approach by correctly identifying the components in a known mixture and the discriminating components in a spiked mixture. Finally, we demonstrate an application of this approach with a brief analysis of the Escherichia coli metabolome. By systematically cataloguing conserved metabolite peaks prior to data analysis methods, our approach broadens the scope of metabolomics and facilitates biomarker discovery.

241 citations

Journal ArticleDOI
TL;DR: Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology - a systems biology approach.
Abstract: The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology - a systems biology approach.

151 citations

Journal ArticleDOI
TL;DR: This paper presents a meta-analyses of the immune system’s response to chemotherapy and shows clear patterns of decline in the number of immune-related adverse events in patients treated with chemotherapy and in the general population.
Abstract: Jerome Amir Singh1,2 & Abdallah S Daar3 1CAPRISA, Private Bag X7, Congella, 4013, Durban, South Africa, and Howard College School of Law, University of KwaZulu-Natal, King George V Avenue, Durban, South Africa. 2Department of Public Health Sciences and Joint Center for Bioethics, University of Toronto, 88 College Street, Toronto, Canada. 3McLaughlin-Rotman Centre for Global Health, Program on Life Sciences, Ethics and Policy, University Health Network; McLaughlin Centre for Molecular Medicine at University of Toronto, MaRS Centre, South Tower, 101 College Street, Suite 406 Toronto, Ontario, Canada M5G 1L7. e-mail: Singhj9@ukzn.ac.za

102 citations

Journal ArticleDOI
TL;DR: This review summarizes contributions that metabolomics has made in cancer research and presents the current challenges and potential future directions within the field.
Abstract: The first discovery of metabolic changes in cancer occurred almost a century ago. While the genetic underpinnings of cancer have dominated its study since then, altered metabolism has recently been acknowledged as a key hallmark of cancer and metabolism-focused research has received renewed attention. The emerging field of metabolomics - which attempts to profile all metabolites within a cell or biological system - is now being used to analyze cancer metabolism on a system-wide scale, painting a broad picture of the altered pathways and their interactions with each other. While a large fraction of cancer metabolomics research is focused on finding diagnostic biomarkers, metabolomics is also being used to obtain more fundamental mechanistic insight into cancer and carcinogenesis. Applications of metabolomics are also emerging in areas such as tumor staging and assessment of treatment efficacy. This review summarizes contributions that metabolomics has made in cancer research and presents the current challenges and potential future directions within the field.

92 citations

Journal ArticleDOI
TL;DR: A generic motif discovery algorithm (Gemoda) for sequential data that can be applied to any dataset with a sequential character, including both categorical and real-valued data and deterministically discovers motifs that are maximal in composition and length.
Abstract: Motivation: Motif discovery in sequential data is a problem of great interest and with many applications. However, previous methods have been unable to combine exhaustive search with complex motif representations and are each typically only applicable to a certain class of problems. Results: Here we present a generic motif discovery algorithm (Gemoda) for sequential data. Gemoda can be applied to any dataset with a sequential character, including both categorical and real-valued data. As we show, Gemoda deterministically discovers motifs that are maximal in composition and length. As well, the algorithm allows any choice of similarity metric for finding motifs. Finally, Gemoda's output motifs are representation-agnostic: they can be represented using regular expressions, position weight matrices or any number of other models for any type of sequential data. We demonstrate a number of applications of the algorithm, including the discovery of motifs in amino acids sequences, a new solution to the (l,d)-motif problem in DNA sequences and the discovery of conserved protein substructures. Availability: Gemoda is freely available at http://web.mit.edu/bamel/gemoda Contact: [email protected] Supplementary Information: Available at http://web.mit.edu/bamel/gemoda

85 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
08 Oct 2012-PLOS ONE
TL;DR: A new algorithm, PROVEAN (Protein Variation Effect Analyzer), is developed, which provides a generalized approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions, and in-frame insertions and deletions.
Abstract: As next-generation sequencing projects generate massive genome-wide sequence variation data, bioinformatics tools are being developed to provide computational predictions on the functional effects of sequence variations and narrow down the search of casual variants for disease phenotypes. Different classes of sequence variations at the nucleotide level are involved in human diseases, including substitutions, insertions, deletions, frameshifts, and non-sense mutations. Frameshifts and non-sense mutations are likely to cause a negative effect on protein function. Existing prediction tools primarily focus on studying the deleterious effects of single amino acid substitutions through examining amino acid conservation at the position of interest among related sequences, an approach that is not directly applicable to insertions or deletions. Here, we introduce a versatile alignment-based score as a new metric to predict the damaging effects of variations not limited to single amino acid substitutions but also in-frame insertions, deletions, and multiple amino acid substitutions. This alignment-based score measures the change in sequence similarity of a query sequence to a protein sequence homolog before and after the introduction of an amino acid variation to the query sequence. Our results showed that the scoring scheme performs well in separating disease-associated variants (n = 21,662) from common polymorphisms (n = 37,022) for UniProt human protein variations, and also in separating deleterious variants (n = 15,179) from neutral variants (n = 17,891) for UniProt non-human protein variations. In our approach, the area under the receiver operating characteristic curve (AUC) for the human and non-human protein variation datasets is ∼0.85. We also observed that the alignment-based score correlates with the deleteriousness of a sequence variation. In summary, we have developed a new algorithm, PROVEAN (Protein Variation Effect Analyzer), which provides a generalized approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions, and in-frame insertions and deletions. The PROVEAN tool is available online at http://provean.jcvi.org.

2,533 citations

Journal ArticleDOI
TL;DR: This paper introduces UpSet, a novel visualization technique for the quantitative analysis of sets, their intersections, and aggregates of intersections, focused on creating task-driven aggregates, communicating the size and properties of aggregates and intersection, and a duality between the visualization of the elements in a dataset and their set membership.
Abstract: Understanding relationships between sets is an important analysis task that has received widespread attention in the visualization community. The major challenge in this context is the combinatorial explosion of the number of set intersections if the number of sets exceeds a trivial threshold. In this paper we introduce UpSet, a novel visualization technique for the quantitative analysis of sets, their intersections, and aggregates of intersections. UpSet is focused on creating task-driven aggregates, communicating the size and properties of aggregates and intersections, and a duality between the visualization of the elements in a dataset and their set membership. UpSet visualizes set intersections in a matrix layout and introduces aggregates based on groupings and queries. The matrix layout enables the effective representation of associated data, such as the number of elements in the aggregates and intersections, as well as additional summary statistics derived from subset or element attributes. Sorting according to various measures enables a task-driven analysis of relevant intersections and aggregates. The elements represented in the sets and their associated attributes are visualized in a separate view. Queries based on containment in specific intersections, aggregates or driven by attribute filters are propagated between both views. We also introduce several advanced visual encodings and interaction methods to overcome the problems of varying scales and to address scalability. UpSet is web-based and open source. We demonstrate its general utility in multiple use cases from various domains.

1,332 citations

Journal ArticleDOI
TL;DR: This paper reflects on the combined experience of conducting twenty-one design studies, conducts an extensive literature survey of related methodological approaches that involve a significant amount of qualitative field work, and compares design study methodology to that of ethnography, grounded theory, and action research.
Abstract: Design studies are an increasingly popular form of problem-driven visualization research, yet there is little guidance available about how to do them effectively. In this paper we reflect on our combined experience of conducting twenty-one design studies, as well as reading and reviewing many more, and on an extensive literature review of other field work methods and methodologies. Based on this foundation we provide definitions, propose a methodological framework, and provide practical guidance for conducting design studies. We define a design study as a project in which visualization researchers analyze a specific real-world problem faced by domain experts, design a visualization system that supports solving this problem, validate the design, and reflect about lessons learned in order to refine visualization design guidelines. We characterize two axes - a task clarity axis from fuzzy to crisp and an information location axis from the domain expert's head to the computer - and use these axes to reason about design study contributions, their suitability, and uniqueness from other approaches. The proposed methodological framework consists of 9 stages: learn, winnow, cast, discover, design, implement, deploy, reflect, and write. For each stage we provide practical guidance and outline potential pitfalls. We also conducted an extensive literature survey of related methodological approaches that involve a significant amount of qualitative field work, and compare design study methodology to that of ethnography, grounded theory, and action research.

704 citations