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 School of Interdisciplinary Informatics University of Nebraska at Omaha, Omaha, NE, 68182 USA November 2015 1 / 21
Space Flight Adds Stress To Protein 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 1 / 21
Houston, We have a Problem! 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 2 / 21
This is Houston: We Also Have the Same Problem!! Introduction Stresses and Proteins The Research Question Results Conclusions Thanks To 3 / 21
Love is a spirit all compact of fire... Venus and Adonis, Shakespeare Introduction Stresses and Proteins The Research Question Results Conclusions Thanks To Fire oxidizes material by chemically combining it with oxygen. Stress from Oxidation at cellular level Protein Oxidizers and “Burners” Free Radials (FR) Reactive Oxygen Species (ROS) 4 / 21
Another Circle of Life... Introduction Stresses and Proteins The Research Question Results Conclusions Thanks To Normal proteins threatened by stress Normal function disabled Protein malfunction 5 / 21
Protein Stress Response A rapid method for protein structure alteration Introduction Stresses and Proteins The Research Question Results Conclusions Thanks To The post-translational modifications (PTMs) may modify protein conformation for adaptation to stress Modified proteins continue function Elapse of stress, PTMs restore original conformations 6 / 21
Our Main Interest How are stresses, proteins (Mt and nonMt) and PTMs related? Introduction The Research Question The problem During a stress response... Method Results What stresses are involved? Conclusions What proteins are involved? Thanks To 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 of proteins which are associated with Alzheimer’s, Diabetes, Parkinson’s (ailments) and Apoptosis 7 / 21
Finding Relationships Introduction The Research Motivation: Strong links exist between stresses, protein Question The problem failure and malfunction and the onsets of ailments, Method according to the literature Results Conclusions These relationships may help to understand the onset of ailments Thanks To 8 / 21
Scattered Knowledge Across Articles Introduction Obstructions to Determining Relationships The Research Question The problem Studying stress response systems using PTMs is a still a young Method science Results Few studies directly detailing these relationship systems Conclusions Response systems mentioned in diverse articles Thanks To 9 / 21
Text Mining to Find Detail Introduction The Research Question The problem Method Our Solution to Obtaining Response System Details Results Conclusions Other text mining software did not handle the large corpus Thanks To or did not have the analysis we required 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 10 / 21
Relationships by Text Mining Introduction The Research Question Complete List of proteins (gene symbols) taken from our The problem Method previous work Results Results: We chose only gene symbols associated to studies Conclusions of Alzheimer’s and Parkinson’s, according to literature Thanks To Stresses PTMs Protein Symbols carbonylation acetylation suox Cold/Heat shock glycosylation supv31 microgravity methylation suv3 oxidation phosphorylation syne2 saline oxidation taco1 etc. etc. etc. 11 / 21
Extract All Relationship Details From Literature Introduction The Research Question The problem Method Results Conclusions Thanks To 12 / 21
Assemble Scattered Knowledge Introduction The Research Question The problem Method Database Support Results Conclusions Results from Lister are stored in a database (Sqlite3) Thanks To 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 13 / 21
We Determine Direct Relationships Stress, Protein and PTM Relationships From Single Articles Introduction The Research Question The problem Method Results Conclusions Thanks To 14 / 21
We Determine Indirect Relationships Stress, Protein and PTM Relationships From Multiple Articles Introduction The Research Question The problem Method Results Conclusions Thanks To 15 / 21
Alzheimer’s: Mt, Stressed Proteins and PTMs Direct relationships: cliques are created from one article Introduction The Research Question Results Conclusions Thanks To Nodes: Yellow : PTMs, Red : Proteins, Blue : Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 16 / 21
Alzheimer’s: nMt, Stressed Proteins and PTMs Direct relationships: cliques are created from one article Introduction The Research Question Results Conclusions Thanks To Nodes: Yellow : PTMs, Red : Proteins, Blue : Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 17 / 21
Parkinson’s: Mt, Stressed Proteins and PTMs Direct relationships: cliques are created from one article Introduction The Research Question Results Conclusions Thanks To Nodes: Yellow : PTMs, Red : Proteins, Blue : Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 18 / 21
Parkinson’s: nMt, Stressed Proteins and PTMs Direct relationships: cliques are created from one article Introduction The Research Question Results Conclusions Thanks To Nodes: Yellow : PTMs, Red : Proteins, Blue : Stresses and Edges indicate that a study exists to combine PTM, Protein and Stress (a clique) 19 / 21
Conclusions 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 20 / 21
Introduction We would like to thank the support students, faculty and staff The Research Question in the UNO-Bioinformatics Core Facility. This project made Results possible by the NASA Nebraska Space Grant (2015-2016). Conclusions Thanks To Thank You! Questions? obonhamcarter@unomaha.edu IS&T Bioinformatics http://bioinformatics.ist.unomaha.edu/ 21 / 21
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