Chapter 16: Text Mining for Translational Bioinformatics

Chapter 16: Text Mining for Translational Bioinformatics

1 Chapter 16: Text Mining for Translational Bioinformatics 2 Overview This presentation is for chapter 16 which discuss : Chapter 16: Text Mining for Translational Bioinformatics 1- terminologies. 2- definitions. 2-uses cases and applications. 3-evaluation techniques and evaluation metrics. 4- linguistic fundamentals. 5-Text mining approaches. 6- text mining tasks. 7- software engineering for Text mining. 3 Terminologies

Mining : is the extraction of valuable minerals or other geological materials from the earth. The word mining could be used in different context to mean different things. In this chapter the word mining is used to refer to finding valuable and useful information in different type of text. Linguistics : is the scientific study of language.There are broadly three aspects to the study, which include language form, language meaning, and language in context. Data mining (the analysis step of the "Knowledge Discovery in Databases" process, or KDD),[1] an interdisciplinary subfield of computer science,[2][3][4] is the computational process of discovering patterns in large data sets involving methods at the intersection

of artificial intelligence, machine learning, statistics, and database systems.[2] The overall goal of the data mining process is to extract information from a data set and transform it into an understandable structure for further use 4 Terminologies Parsing or syntactic analysis: is the process of analysing a string of symbols, either in natural language or in computer languages, according to the rules of a formal grammar. The term parsing comes from Latin pars (orationis), meaning part (of speech).[1][2] Translational Bioinformatics (TBI): is an emerging field in health informatics, focused on the convergence of molecular biostatistics, statistical genetics, and clinical informatics. BioNLP : BioNLP.org exists to help researchers in their work on natural language processing (NLP) for articles in the biomedical literature.

Natural language processing (NLP): is a field of computer science, artificial intelligence, and linguistics concerned with the interactions between computers and human (natural) languages. As such, NLP is related to the area of humancomputer interaction the study of bioinformatics, 5 Text Mining for Translational Bioinformatics is a new field with tremendous research potential. It is a subfield of biomedical natural language processing that concerns itself directly with the problem of relating basic biomedical research to clinical practice, and vice versa. 6

What are the applications of Text Mining Translational research refers to two distinct domains: T1 research, the bench-to-bedside enterprise of translating knowledge from the basic sciences into the development of new treatments. T2 research, translating the findings from clinical trials into everyday practice public health 7 Potential use cases Text Mining for Translational Bioinformatics The foundational question in text mining for translational bioinformatics

is what the use cases are ? The answer lies at least in: 1- in the nature of the specific kinds of information that text mining should try to gather. 2- the uses to which that information is intended to be put. 8 A definition for use cases for text mining for translational bioinformatics One step in the direction of a definition for use cases for text mining for translational bioinformatics is

1- determining classes of information found in clinical text that would be useful for basic biological scientists. 2 - classes of information found in the basic science literature that would be of use to clinicians. BioNLP : which tend to focus either on finding biological information for biologists, or on finding clinical information for clinicians. it is likely that there is no single set of data that would fit the needs of biological scientists on the one hand or clinicians on the other, and that information needs will have to be defined on a bespoke basis for any given translational bioinformatics task. 9 Potential applications 1- better phenotyping

Phenotype : is All the observable characteristics of an organism, such as shape, size, color, and behavior, that result from the interaction of its genotype (total genetic makeup) with the environment. A phenotype : is the entirety of observable characteristics of an organism [7]. The wide range and rapidly changing technologies for measuring observable features of patient phenotypes require the text mining user to be very specific about what observables they want to capture. For example, phenotypes can include any behavior, ranging from duration of mating dances in flies to alcohol-seeking in humans. They can also include any measurable physical characteristic When phenotyping is too broad, the genetic association may be obscured by variability in the patient population. strict phenotyping of patients improves the ability to find disease genes.

10 meta-analysis meta-analysis : refers to methods that focus on contrasting and combining results from different studies Another use for text mining in translational bioinformatics is aiding in the preparation of Cochrane reviews and other meta-analyses of experimental studies. text mining could be used to identify cohorts that should be included in the meta-analysis, as well as to determine P-values and other indicators of significance levels. 11 The pharmacogenomics

perspective One area of research that has made some steps towards defining a use case for text mining is pharmacogenomics. One example is : The PharmGKB: it is a pharmacogenomics knowledge resource that encompasses clinical information including dosing guidelines and drug labels, potentially clinically actionable gene-drug associations and genotype-phenotype relationships. Essential elements of their definition of pharmacogenomics text mining include finding relationships between genotypes, phenotypes, and drugs. 12

The pharmacogenomics perspective first step the ability to find mentions of the semantic types of interest when they are mentioned in text. These will be of increasing utility if they can be mapped to concepts in a controlled vocabulary. Each semantic type presents unique challenges. For example, finding information about genotypes requires finding mentions of genes (see Section 4.3 below), finding mentions of mutations and alleles, and mapping these to each other; finding mentions of drugs, which is more difficult than it is often assumed to be [6]; and finding mentions of phenotypes. 13

PharmGKB 14 The pharmacogenomics perspective There is some evidence from the PharmGKB and the Comparative Toxicogenomics Database experiences : text mining can scale up processing in terms of the number of diseases studied and the number of gene-disease, drug-disease, and drug-gene associations discovered experiments with the PharmGKB

database suggest that pharmacogenomics is currently more powerful than genomics for finding such associations and has reached the point of being ready for translation of research results to clinical practice 15 Informatics for Integrating Biology and the Bedside (i2b2) prospective (i2b2) is a National Center for Biomedical Computing devoted to translational bioinformatics. It has included text mining within its scope of research areas. i2b2's focus has been on extracting information from free text in clinical

records. Towards this end, i2b2 has sponsored shared tasks on deidentification of clinical documents, determining smoking status, detecting obesity and its comorbidities, medical problems, treatments, and tests. Note that there are no genomic components to this data. 16 Text Mining, Natural Language Processing, and Computational Linguistics Text mining, natural language processing, and computational linguistics are often used interchangeably. However some differences exist between them. Computational linguistics is strictly defined: it deals with building computationally testable models of human linguistic behavior ed more or less interchangeably. Natural language processing has to do with building a wide range of

applications that take natural language as their input. Text mining is more narrow than natural language processing: it deals with the construction of applications that provide a solution to a specific information need 17 Text Mining, Natural Language Processing example For example, a syntactic analyzer would be an example of a natural language processing application. a text mining application might use that syntactic analyzer as part of the process for filling the very specific information need of finding information about protein-protein interactions 18

Evaluation Techniques and Evaluation Metrics in Text Mining Corpora: One paradigm of evaluation in text mining is based on the assumption that all evaluation should take place on naturally occurring texts. These texts are annotated with data or metadata about what constitutes the right answers for some task. For example: if the intended application to be tested is designed to locate mentions of gene names in free text, then the occurrence of every gene name in the text would be marked. The mark-up is known as annotation. (Note that this is a very different use of the word annotation from its use in

the model organism database construction community.) The resulting set of annotated documents is known as a corpus (plural corpora). 19 corpus Given a corpus, an application is judged by its ability to replicate the set of annotations in the corpus. Some types of corpora are best built by linguists, e.g., those involving syntactic analysis, but there is abundant evidence that biomedical scientists can build good corpora if they follow best practices in corpus design. 20 2-Structured test suites. Structured test suites are built on the principles of software testing.

contain groups of inputs that are classified according to aspects of the input. For example: a test suite for applications that recognize gene names might contain sentences with gene names that end with numbers, that do not end with numbers, that consist of common English words, or that are identical to the names of diseases 21 3- Metrics Metrics.

A small family of related metrics is usually used to evaluate text mining systems. Accuracy: the number of correct answers divided by the total number of answers, is rarely used. Precision: is defined as the number of correct system outputs (true positives, or TP) divided by the total number of system outputs (the count of TP plus the false positives (FP) erroneous system outputs). Recall is defined as the number of true positives divided by the total number of potential system outputs, i.e. true positives plus false negatives (FN) things that should have been output by the system, 22

Metrics Precision = recall = + + 23 Metrics Balanced F-measure: The balanced F-measure attempts to reduce precision and recall to a single measure. It is calculated as the harmonic mean of precision and recall

= ( 2 +1) 2 + 24 Linguistic Fundamentals Building applications for text mining for translational bioinformatics is made easier by some understanding of the nature of linguistic structure. Two basic principles are relevant: 1- One is that linguistic structure consists of multiple layers.

2- The other is that every layer of linguistic structure is characterized by ambiguity. Structural linguistics thus involves collecting a corpus of utterances and then attempting to classify all of the elements of the corpus at their different linguistic levels: the phonemes, morphemes, lexical categories, noun phrases, verb phrases, and sentence types 25 Linguistic Fundamentals an utterance : is a smallest unit of speech. It is a continuous piece of speech beginning and ending with a clear pause. In the case of oral languages, A phoneme: is a basic unit of a language's phonology, which is combined

with other phonemes to form meaningful units such as words or morphemes. The phoneme can be described as "The smallest contrastive linguistic unit which may bring about a change of meaning".[1] In this way the difference in meaning between the English words kill and kiss is a result of the exchange of the phoneme /l/ for the phoneme /s/. All linguistic analyses in text mining are descriptive in nature. That is, they seek only to describe the nature of human linguistic productions, much as one might attempt to describe the multi-dimensional structure of a protein 26 2.1 Layers of Linguistic Structure The layers of linguistic structure vary somewhat between written and spoken language (although many are shared). We focus here on the layers that are relevant to written language, focusing particularly on scientific journal articles and on clinical

documents. 27 Document structure The first layer of the structure of written documents that is relevant to text mining for translational bioinformatics is the structure of individual documents. In the case of journal articles : it consists of all of the division of the document into discrete sections, typically in what is known as the IMRD model the IMRD model consist of:

an abstract, introduction, methods section, results section, discussion, and bibliography. Acknowledgments may be present, as well. 28 Document structure The ability to segment a document into these sections is important because different sections often require different processing techniques and because different sections should be focused on for different types of information. For example: methods sections are frequent sources of false positives for various semantic classes, which led researchers to ignore them in much early research. However, they are also fruitful sections for finding information

about experimental methods, and as it has become clear that mining information about experimental methods is important to biologists. 29 Document structure it has become clear that methods must be developed for dealing with methods sections. Abstracts section: has been shown to have different structural and content characteristics from article bodies [17]; most research to date has focused on abstracts, and it is clear that new approaches will be required to fully exploit the information in article bodies. 30

Document structure Segmenting and labeling document sections can be simple when documents are provided in XML and a DTD is available. However, this is often not the case; for instance, many documents are available for processing only in HTML format. In this situation, two topics exist: 1-finding the boundaries of the sections, 2-labelling the sections.

The latter is made more complicated by the fact that a surprising range of phrases are used to label the different sections of a scientific document. For example: the methods section may be called Methods, Methods and Materials, Materials and Methods, Experimental Procedures, Patients and Methods, Study Design, etc. 31 Document structure Clinical documents present a far more complex set of challenges than even scientific journal articles. For one thing, there is a much wider range of clinical document typesadmission notes, discharge summaries, radiology report an iterative procedure for building a segmenter for a range of clinical

document types.s, pathology reports, office visit notes, etc. 32 Sentences in a document Once the document has been segmented into paragraphs, the paragraphs must be further segmented into sentences. Sentence segmentation is a surprisingly difficult task. Even for newswire text. Two main difficulties arise. 1- it is the fact that the function of periods is ambiguousthat is, a period may serve more than one function in a written text, such as marking the end of an abbreviation (Dr.), marking the individual letters of an abbreviation (p.r.n.), indicating the rational parts of real numbers (3.14), and so on.

2- some of the expected cues to sentence boundaries are absent in biomedical text. For example: in texts about molecular biology, it is possible for a sentence to begin with a lower-case letter when a mutant form of a gene is being mentioned. Various approaches have been taken to the sentence segmentation task 33 Sentence segmentation Various approaches have been taken to the sentence segmentation task. The KeX/PROPER system [20] uses a rule-based approach. The LingPipe system provides a popular machine-learning-based approach through its LingPipe API. Its model is built on PubMed/MEDLINE documents and works well for journal articles, but it is not likely to work well for clinical text (although this has not been evaluated).

In clinical documents, it is often difficult to define any notion of sentence at all. 34 Tokens Written sentences are built up of tokens. Tokens include words, but also punctuation marks, in cases where those punctuation marks should be separated from words that they are attached to. The process of segmenting a sentence into tokens is known as tokenization The case of hyphens is even more difficult. Hyphens may have several functions in biomedical text. If they indicate the absence of a symptom (e.g., -fever), they should probably be separated, since they have their own meaning, indicating the absence of the symptom. On the other hand, they should remain in place when separating parts of a word, such as up-regulate.

35 stems For some applications, it is advantageous to reduce words to stems or lemmata. Stems are normalized forms of words that reduce all inflected forms to the same string. They are not necessarily actual words themselves for example, the stem of city and cities is citi, which is not a word in the English language.

Their utility comes in applications that benefit from this kind of normalization without needing to know exactly which words are the rootsprimarily machine-learning-based applications. 36 lemmata The term lemma (plural lemmata) is overloaded. It can mean the root word that represents a set of related words. For example, the lemma of the set {phosophorylate, phosphorylates, phosphorylated, phosphorylating} is phosphorylate Lemmas have a clear advantage of stems for some applications. However, while it is always possible to determine the stem of a word (typically using a rule-based approach, such as the Porter stemmer [21],

it is not always possible to determine the lemma of a word automatically. The BioLemmatizer [22] is a recently released tool that shows high performance on the lemmatization task. 37 lexical category It is often useful to know the part of speech, technically known as lexical category of the tokens in a sentence Parts of speech are typically assigned to tokens by applications called part of speech taggers. Part of speech tagging is made difficult by the fact that many words are

ambiguous as to their part of speech. For example, in medical text, the word cold can be an adjective or it can be a reference to a medical condition. A word can have several parts of speech, e.g. A variety of part of speech taggers that are specialized for biomedical text exist, including MedPOST [23], LingPipe, and the GENIA tagger 38 Syntactic structure The syntactic structure of a sentence: is the way in which the phrases of the sentence relate to each other. For example, in the article title Visualization of bacterial glycocalyx with a scanning electron microscope, the phrase with a scanning electron microscope is associated with visualization, not with bacterial glycocalyx.

Automatic syntactic analysis is made difficult by the existence of massive ambiguity. For example: while one possible interpretation of that title is that the visualization is done with a scanning electron microscope, another possible interpretation is that the bacterial glycocalyx has a scanning electron microscope 39 Syntactic analysis is very easy for humans to determine which interpretation of the article title is correct. However, it is very difficult for computers to make this determination. There are many varieties of syntactic ambiguity, and it is

likely that any nontrivial sentence contains at least one. Syntactic analysis is known as parsing. The traditional approach to automated syntactic analysis attempts to discover the phrasal structure of a sentence, as described above. A new approach called dependency parsing focuses instead on relationships between individual words. It is thought to better reflect the semantics of a sentence, and is currently popular in BioNLP 40 The Two Families of Approaches: Rule-Based and Learning-Based There are two basic approaches to text mining:

1- rule-based, also known as knowledge. Rule-based approaches to text mining are based on the application of rules. typically manually constructed, to linguistic inputs. For example : a rule-based approach might specify that in the pattern A X noun the X is an adjective, while in the pattern The adjective X verb the X is a noun, allowing us to differentiate between the word cold as an adjective in the former case and as a medical condition in the latter case. Rule-based solutions can be constructed for all levels of linguistic analysis. 41

The Two Families of Approaches: Machine-learning-based approaches Machine-learning-based approaches to text mining are based on an initial step of feeding the system a set of data that is labelled with the correct answers, be they parts of speech for tokens or the locations of gene names in text. The job of the system is then to figure out cues that indicate which of the ambiguous analyses should be applied. For instance, a system for document classification may learn that if a document contains the word murine, then it is likely to be of interest to researchers who are interested in mice Many different algorithms for machine learning exist, but the key to a successful system is the set of features that are used to perform the classification. For example, a part of speech tagger may use the apparent parts of speech of the two preceding words as a feature for deciding the part of speech of a third word. 42

The Two Families of Approaches: Machine-learning-based approaches It is often claimed that machine learning systems can be built more quickly than rule-based systems due to the time that it takes to build rules manually. However, building feature extractors is time-consuming, and building the labelled training data with the right answers is much more so. There is no empirical support for the claim that learning-based systems can be built more quickly than rule-based systems. Furthermore, it is frequently the case that putative learning-based systems actually apply rules in pre- or post-processing steps, making them hybrid systems. 43 Text Mining Tasks Information retrieval

Document classification Named entity recognition Named entity normalization Relation or information extraction Question-answering Summarization 44

Information Retrieval Information retrieval is the task of, given an information need and a set of documents, finding the documents that are relevant to filling that information need. PubMed/MEDLINE is an example of a biomedical information retrieval system for scientific journal articles Google is an information retrieval system for web pages. Early information retrieval assumed that all documents were classified with some code and typically required the assistance of a librarian to determine the appropriate code of interest. 45

Information Retrieval Keyword-based retrieval, in which the user enters a set of words that a relevant text would be expected to contain and the content of the texts in the set of documents are searched for those words, was a revolution made possible by the introduction of computers and electronic forms of documents in the hospital or research environment. The naive approach to keyword-based retrieval simply checks for the presence or absence of the words in the query, known as boolean search 46 Information Retrieval Modern approaches use relatively simple mathematical techniques to determine :

(a) the relative importance of words in the query in deciding whether or not a document is relevantthe assumption here is that not all words are equally important. (b) how well a given word reflects the actual relevance of a given document to the query For example, we can determine, given a count of how often the words hypoperfusion and kidney occur in the set of documents as a whole, that if we are looking for documents about kidney hypoperfusion, we should give more weight to the rarer of the two words; given a count of how often the words kidney and hypoperfusion occur in two documents, we can determine which of the two documents is most relevant to the query. 47

Document Classification Document classification is the task of classifying a document as a member of one or more categories. Document classification typically uses very simple feature sets, such as the presence or absence of the words from the training data. When this is the only feature, it is known as a bag of words representation. However, it has also been found useful to use more abstract, conceptual features. For example, [25] found the presence or absence of mentions of mouse strains to be a useful feature, regardless of the identity of the particular strain 48

Named Entity Recognition Named entity recognition is the task of finding mentions of specific semantic classes in a text. In general language processing, the most heavily studied semantic classes have been persons, places, and organizationsthus, the term named entity. In genomic BioNLP, the most heavily studied semantic class has been gene and protein names. However, other semantic classes have been studied as well, including cell lines and cell types. Early results in named entity recognition were consistent with the hypothesis that this task could not be achieved by simply starting with a dictionary of gene names and looking for those gene names in text.

49 Named Entity Recognition At least three problems were immediately evident with this approach 1- the fact that new gene names are coined constantly 2- the fact that a number of gene names are homographs of common English words, 3- the fact that many genes have names or synonyms that are unhelpful, such as putative oxidoreductase (Entrez Gene ID 6393330)

However, recent evidence has suggested that dictionary-based approaches can achieve moderate success if the dictionary and the data to be processed are subjected to extensive preprocessing. 50 Named Entity Normalization Named entity normalization is the process of taking a mention of a named entity in free text and returning a specific database identifier that it refers to it. In the biological domain, this has been studied most extensively in the case of genes and proteins, and the corresponding task is known as gene normalization There are two major problems in gene normalization.

The first is that many species have genes with the same name. For example, the BRCA1 gene is found in an enormous number of animals. Thus, finding the appropriate gene identifier requires knowing the species under discussion, which is a research problem in itself. 51 Named Entity Normalization The other problem is that a single species may have multiple genes with the same name. For example, humans have five genes named TRP-1. Gene normalization is often approached as a problem in word sense disambiguation. A popular approach to this utilizes knowledge about the gene and the context in which the gene is mentioned.

For example: the SUMMARY fields of the candidate genes might be used as a source of words that indicate what we know about the gene. Then, if we see the words cation and channel in the text surrounding the gene name, we should expect that we have an instance of the TRP1 with Entrez Gene ID 7220 52 Relation or Information Extraction Information extraction, or more recently relation extraction, is the process of mining very specific types of facts from text. Information extraction systems are by definition restricted to a very specific type of

information. For example, a typical genomic information extraction system might extract assertions about protein-protein interactions, or a clinical information extraction system might mine assertions about relationships between diseases and their treatments Rule-based approaches use typical sentence patterns. These may consist of text literals or may involve syntactic analyses [32]. Learning-based approaches have classically used bag-of-words representations (see Section 4.2), but more recent approaches have had success using features taken from syntactic analysis, particularly dependency parsing [33]. 53

Question-Answering Task Question-answering is the task of taking a question and a source of information as input and returning an answer. Early approaches to question-answering assumed that the source of information was a database, but modern approaches assume that the answer exists in some PubMed/ MEDLINE document or (for non-biomedical applications) in some web page. Question-answering differs from information retrieval in that the goal is to return a specific answer, not a document containing the answer. It differs from information extraction in that it is meant to allow for ad hoc queries, while information extraction focuses on very specific information needs.

Question-answering typically involves determining the type of answer that is expected (a time? a location? a person?), formulating a query that will return documents containing the answer, and then finding the answer within the documents that are returned. 54 Question-Answering Task Various types of questions have varying degrees of difficulty. The best results are achieved for so-called factoid questions, such as where are lipid rafts located?, while why questions are very difficult. The medical domain presents some unique challenges. For example, questions beginning with when might require times as their answer (e.g., when does blastocyst formation occur in humans?

but also may require very different sorts of answers, e.g.,when should antibiotics be given for a sore throat? [37]. 55 Summarization Summarization is the task of taking a document or set of documents as input and returning a shorter text that conveys the information in the longer text(s). * There is a great need for this capability in the biomedical domaina search in PubMed/MEDLINE for the gene p53 returns 56,464 publications as of the date of writing. In the genomics domain, there have been major areas of summarization research.

1- is the automatic generation of GeneRIFs. GeneRIFs are short text snippets, less than 255 characters in length, associated with specific Entrez Gene entries. Typically they are manually cut-and-pasted from article abstracts. 2-is finding the best sentence for asserting a protein-protein interaction. This task was made popular by the BioCreative shared task. The idea is to boil down a set of articles to the single sentence that best gives evidence that the interaction occurs. Again, 56 Software Engineering for Text Mining Like all translational bioinformatics software, text mining software for translational bioinformatics can be considered health-critical and should be subject to the strictest standards of quality assurance and software testing.

The special requirements of software testing for natural language processing applications are not covered in the standard books on software testing. There are two basic paradigms for evaluating text mining applications 57 Software Engineering for Text Mining 1- The standard paradigm involves running large corpora through the application and determining the F-measure achieved. However, this approach is not satisfactory for quality assurance and software testing. It is good for achieving overall estimates of performance, but does a poor job of indicating what the application is good at and what it is bad at.

For this task, structured test suites and application of the general principles of software testing are much more appropriate.. It is helpful to consult with a descriptive linguist when designing test suites for assessing an application's ability to handle linguistic phenomena 58 Software Engineering for Text Mining Some researchers presented a quantitative examination of the effectiveness of corpora versus structured test suites for software testing, and demonstrates that structured test suites achieve better code coverage (percentage of code that is executed during the test phasebugs cannot be discovered in code that is not executed.

User interface assessment requires special techniques not found in other areas of software testing for natural language processing. User interface testing has been most heavily studied in the case of literature search interfaces. 59 reference Chapter 16: Text Mining for Translational Bioinformatics by K. Bretonnel Cohen mail, Lawrence E. Hunter 60

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