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Introduction Stresses and Proteins The Research Question A text mining application for linking functionally Results Conclusions stressed-proteins to their post-translational Thanks To modifications Oliver Bonham-Carter and Dhundy Bastola
Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
Oliver Bonham-Carter and Dhundy Bastola
School of Interdisciplinary Informatics University of Nebraska at Omaha, Omaha, NE, 68182 USA
November 2015
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
Expedition 24, a three month mission: NASA astronaut Tracy Caldwell Dyson and Russian cosmonauts Alexander Skvortsov, and Mikhail Kornienko, Sept 26, 2010 Astronauts suffered onset of cardiovascular and muscular atrophy Muscle weakened by exposure to weightlessness, microgravity (MG) All human and animal missions had results of muscle weaknesses
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
Protein Damage From Stress
Exposure to microgravity
Muscle tissue: reduction of mass and strength Mitochondrial damage: degraded and irregular shape, reduced functionality Loss of function, onset of atrophy Beginnings of cell death and illnesses
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
Venus and Adonis, Shakespeare
Fire oxidizes material by chemically combining it with
Stress from Oxidation at cellular level Protein Oxidizers and “Burners”
Free Radials (FR) Reactive Oxygen Species (ROS)
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
Normal proteins threatened by stress Normal function disabled Protein malfunction
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Introduction
Stresses and Proteins
The Research Question Results Conclusions Thanks To
A rapid method for protein structure alteration
The post-translational modifications (PTMs) may modify protein conformation for adaptation to stress
Modified proteins continue function Elapse of stress, PTMs restore original conformations
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
How are stresses, proteins (Mt and nonMt) and PTMs related?
During a stress response...
What stresses are involved? What proteins are involved? What PTMs are involved? Want to determine how stresses, proteins and PTMs are related, according to the literature In particular, we are studying the stress response systems
Diabetes, Parkinson’s (ailments) and Apoptosis
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Motivation: Strong links exist between stresses, protein failure and malfunction and the onsets of ailments, according to the literature
These relationships may help to understand the onset of ailments
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Obstructions to Determining Relationships
Studying stress response systems using PTMs is a still a young science Few studies directly detailing these relationship systems Response systems mentioned in diverse articles
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Introduction The Research Question
The problem Method
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Our Solution to Obtaining Response System Details
Other text mining software did not handle the large corpus
Lister: Our text mining tool built in Python Used to capture stress, protein and PTM relationships across PubMed literature Supervised system: Keyword driven Abstracts: short, direct pieces of text to summarize a study
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Complete List of proteins (gene symbols) taken from our previous work Results: We chose only gene symbols associated to studies
Stresses PTMs Protein Symbols carbonylation acetylation suox Cold/Heat shock glycosylation supv31 microgravity methylation suv3
phosphorylation syne2 saline
taco1 etc. etc. etc.
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Database Support
Results from Lister are stored in a database (Sqlite3) Each article in PubMed has a unique identification number (PMID)
Found keywords are recorded with PMID number Keywords found in the same articles, also have same article PMID references
When keywords are found in the same article, we have reason to suspect a relationship
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Stress, Protein and PTM Relationships From Single Articles
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Introduction The Research Question
The problem Method
Results Conclusions Thanks To
Stress, Protein and PTM Relationships From Multiple Articles
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Introduction The Research Question Results Conclusions Thanks To
Direct relationships: cliques are created from one article
Nodes: Yellow: PTMs, Red: Proteins, Blue: Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 16 / 21
Introduction The Research Question Results Conclusions Thanks To
Direct relationships: cliques are created from one article
Nodes: Yellow: PTMs, Red: Proteins, Blue: Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 17 / 21
Introduction The Research Question Results Conclusions Thanks To
Direct relationships: cliques are created from one article
Nodes: Yellow: PTMs, Red: Proteins, Blue: Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 18 / 21
Introduction The Research Question Results Conclusions Thanks To
Direct relationships: cliques are created from one article
Nodes: Yellow: PTMs, Red: Proteins, Blue: Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 19 / 21
Introduction The Research Question Results Conclusions Thanks To
Obtained from study: A short listing of proteins (associated with ailments), that are known to react with PTMs when stressed in particular ways Relationships are supported by literature citations This list of actors may describe possible ailment onset conditions
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Introduction The Research Question Results Conclusions Thanks To
We would like to thank the support students, faculty and staff in the UNO-Bioinformatics Core Facility. This project made possible by the NASA Nebraska Space Grant (2015-2016).
IS&T Bioinformatics http://bioinformatics.ist.unomaha.edu/
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