Extracting and Measuring Uncertain Biomedical Knowledge from Scientific Statements

doi:10.2478/jdis-2022-0008

Abstract

Abstract:

Purpose: Given the information overload of scientific literature, there is an increasing need for computable biomedical knowledge buried in free text. This study aimed to develop a novel approach to extracting and measuring uncertain biomedical knowledge from scientific statements.

Design/methodology/approach: Taking cardiovascular research publications in China as a sample, we extracted subject-predicate-object triples (SPO triples) as knowledge units and unknown/hedging/conflicting uncertainties as the knowledge context. We introduced information entropy (IE) as potential metric to quantify the uncertainty of epistemic status of scientific knowledge represented at subject-object pairs (SO pairs) levels.

Findings: The results indicated an extraordinary growth of cardiovascular publications in China while only a modest growth of the novel SPO triples. After evaluating the uncertainty of biomedical knowledge with IE, we identified the Top 10 SO pairs with highest IE, which implied the epistemic status pluralism. Visual presentation of the SO pairs overlaid with uncertainty provided a comprehensive overview of clusters of biomedical knowledge and contending topics in cardiovascular research.

Research limitations: The current methods didn't distinguish the specificity and probabilities of uncertainty cue words. The number of sentences surrounding a given triple may also influence the value of IE.

Practical implications: Our approach identified major uncertain knowledge areas such as diagnostic biomarkers, genetic polymorphism and co-existing risk factors related to cardiovascular diseases in China. These areas are suggested to be prioritized; new hypotheses need to be verified, while disputes, conflicts, and contradictions need to be settled.

Originality/value: We provided a novel approach by combining natural language processing and computational linguistics with informetric methods to extract and measure uncertain knowledge from scientific statements.

Key words: Uncertain knowledge, Information entropy, Natural language processing, Cardiovascular diseases, China

Xin Guo , Yuming Chen , Jian Du , and Erdan Dong .(2022). Extracting and Measuring Uncertain Biomedical Knowledge from Scientific Statements. Journal of Data and Information Science, 7(2), 6-30. DOI: 10.2478/jdis-2022-0008

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URL: http://manu47.magtech.com.cn/Jwk3_jdis/EN/10.2478/jdis-2022-0008

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Figures/Tables 10

Figure 1.

Table 1.

Figure 2.

Table 2.

Table 3.

Table 4.

Sample sentences from SO pairs with high IE.

Polymorphism, Genetic_Coronary Arteriosclerosis
#	PMID	Year	Predicate	Sentence
1.1	20668462	2010	AFFECTS	To clarify whether polymorphisms of the RAGE gene were related to CAD, we performed a case-control study in Chinese Han patients.
1.2	22363637	2012	AFFECTS	Our findings failed to demonstrate a correlation between (CAG)(n) polymorphism with CAD; however, we concluded that the rare 21bp deletion might have a more compelling effect on CAD than the common (CAG)(n) polymorphism, and MEF2A genetic variant might be a rare but specific cause of CAD/MI.
1.3	22345093	2012	NEG_AFFECTS	The three other polymorphisms of the RAS do not seem to influence the development of CAD in type 2 diabetes.
1.4	23583798	2013	AFFECTS	However, given the limited number of studies and the potential biases, the influence of this (myeloperoxidase (MPO) G463A) polymorphism on CAD risk needs further investigation.
1.5	24155913	2013	CAUSES	Our findings provided strong evidence for the potentially contributory roles of RAGE multiple genetic polymorphisms, especially in the context of locus-to-locus interaction, in the pathogenesis of CAD among northeastern Han Chinese.
1.6	24239227	2014	AFFECTS	Some polymorphisms in the fibroblast growth factor receptor 4 gene (FGFR-4) have been correlated with coronary artery disease, however, the role of polymorphisms in the FGFR-4 gene in ischemic stroke remain unknown.
1.7	27323132	2016	AFFECTS	There is growing evidence that polymorphisms in NOS3 influence the progression of CAD; however, there is also a controversy regarding the association of polymorphisms in the gene encoding NOS3 and CAD.
1.8	30826813	2019	AFFECTS	Studies have reported that inflammatory cytokine interleukin-8 (IL-8) gene -251 A/T (rs4073) polymorphism is correlated with CAD susceptibility, but the result remains controversial.
1.9	31770200	2019	AFFECTS	Thus, a meta-analysis was conducted to reassess the effects of this (interleukin-8 gene) polymorphism on CAD risks.
Hydroxymethylglutaryl-CoA Reductase Inhibitors_Acute Coronary Syndrome
#	PMID	Year	Predicate	Sentence
9.1	19781407	2009	TREATS	Rationale and design of China intensive lipid lowering with statins in acute coronary syndrome: the CHILLAS study.
9.2	23990595	2014	TREATS	The effect of statins in patients with acute coronary syndrome (ACS) at advanced age with lower low-density lipoprotein cholesterol (LDL-C) levels undergoing percutaneous coronary intervention (PCI) remains unknown.
9.3	24216317	2014	TREATS	Results of the current study merit further investigation of the early use of statins in patients with NSTE-ACS to delineate patient subgroups who may benefit from this therapy.
9.4	25879728	2015	TREATS	Combination therapy analysis of ezetimibe and statins in Chinese patients with acute coronary syndrome and type 2 diabetes.
9.5	25879728	2015	TREATS	The effects and safety of the combined treatment of ezetimibe (EZ) and statins in Chinese patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) remain unknown.
9.6	30986750	2019	TREATS	This study aimed to assess use of prehospital statins and LDL-C levels at admission in ACS patients with history of MI or revascularization.
Hyperuricemia_Hypertensive Disease
#	PMID	Year	Predicate	Sentence
10.1	22377586	2012	PREDISPOSES	Multivariate logistic regression showed that age, gender, overweight/obesity, dyslipidemia and alcohol use were risk factors for prehypertension, and age, overweight/obesity, dyslipidemia, alcohol use, family history of hypertension and hyperuricemia were risk factors for hypertension.
10.2	24905962	2014	PREDISPOSES	In addition, after adjusting for potential confounders, hyperuricemia was associated with increased risk of hypertension in both males and females, with odds ratios (95% CI) of 1.680 (1.110-2.543) and 1.065 (1.012-1.118), respectively.
10.3	25437867	2014	PREDISPOSES	Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.
10.4	25863573	2015	PREDISPOSES	Besides traditional risk factors, multiple logistic regression analysis indicated that obesity, diabetes, dyslipidemia, and hyperuricemia were becoming risk factors for hypertension in this rural area. The status of hypertension is grim currently in rural Northeast China.
10.5	25919438	2015	PREDISPOSES	Hyperuricemia is an independent risk factor for hypertension.
10.6	27129957	2016	PREDISPOSES	A Kaplan-Meier survival analysis showed that hyperuricemia predicted higher incidences of hypertension in a dose-dependent manner: hypertension onset significantly differed across SUA quartiles.
10.7	28176036	2017	PREDISPOSES	Whether hyperuricemia is an independent risk factor for hypertension in adults is still under debate.
10.8	28808071	2017	PREDISPOSES	Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension.
10.9	28808071	2017	PREDISPOSES	Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown.
10.10	29390287	2017	PREDISPOSES	HUA was also a risk factor for hypertension in this age group (odds ratio 1.425, 95% confidence interval, 1.217-1.668, P <.001).
10.11	28445311	2017	PREDISPOSES	Besides, after adjustment for confounding variables, hyperuricemia was associated with an increased risk of hypertension in both male and female patients, with odds ratios of 2.152 (95% confidence interval 1.324-3.498) and 2.133 (95% confidence interval 1.409-3.229), respectively.
10.12	28445311	2017	PREDISPOSES	Hyperuricemia was significantly associated with the risk of hypertension.
10.13	30817449	2019	PREDISPOSES	This study aimed to develop a cumulative score composed of seven risk factors: age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and impaired estimated glomerular filtration rate (eGFR), to evaluate the risk of new-onset hypertension.
10.14	31908434	2019	AFFECTS	Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke.

Table 4.

Figure 3.

Figure 4.

Table 5.

Examples of uncertain sentences and triples from different parts of scientific statements.

Statement Location	Supporting Sentences	SPO Triples
Premise (Background)	Liver X receptors (LXRs) play a central role in atherosclerosis; however, LXR activity of organic pollutants and associated potential risk of atherosclerosis have not yet been characterized.	liver X receptor _AFFECTS_ Atherosclerosis
Premise (Background)	Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a risk factor for acute coronary syndrome (ACS), but this remains controversial.	Phospholipase A2 _PREDISPOSES_ Acute coronary syndrome
Hypothesis (Objective)	We therefore performed a case-control study investigating the possible relation between ACE gene polymorphisms and MVPS in Taiwan Chinese.	Mitral Valve Prolapse _ASSOCIATED_WITH_ gene polymorphism
Hypothesis (Objective)	Given the uncertainty regarding the relationship of C-reactive protein (CRP) and homocysteine (Hcy) to atherosclerotic burden, our aim was to determine whether CRP and Hcy are related to the presence of subclinical coronary plaque and stenosis.	Stenosis _ASSOCIATED_WITH_ C-reactive protein Stenosis _ASSOCIATED_WITH_ homocysteine
Evidence (Results)	Ischemic heart disease was identified as the possible etiology of HF in a greater proportion of non-Chinese patients (47.7% vs. 35.3%; p < 0.001) whereas hypertension (26.1% vs. 16.1%; p < 0.001) and valvular heart disease (11.6% vs. 7.2%; p < 0.001) were relatively more common in Chinese patients.	Myocardial Ischemia _CAUSES_ Heart failure
Evidence (Results)	Genetic polymorphisms of four genes, methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein E (ApoE) have been demonstrated to associate with the increased risk for both MDD and stroke, while the association between identified polymorphisms in angiotensin-converting enzyme (ACE) and serum paraoxonase (PON1) with depression is still under debate, for the existing studies are insufficient in sample size.	Peptidyl-Dipeptidase A _PREDISPOSES_ Cerebrovascular accident Peptidyl-Dipeptidase A _PREDISPOSES_ Major Depressive Disorder Arylesterase _PREDISPOSES_ Cerebrovascular accident Arylesterase _PREDISPOSES_ Major Depressive Disorder
Claims (Conclusions)	This study shows a significant association of hypertension susceptibility loci only in obese Chinese children, suggesting a likely influence of childhood obesity on the risk of hypertension.	Hypertensive disease _AFFECTS_ Obesity
Claims (Conclusions)	Our data demonstrate that TrkB protects endothelial integrity during atherogenesis by promoting Ets1-mediated VE-cadherin expression and plays a previously unknown protective role in the development of CAD	ETS1 gene, ETS1 _INTERACTS_WITH_ cadherin 5

Table 5.

Figure 5.

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Cue words	Frequency in all SemMedDB sentences		Frequency in our Triples Store sentences
Unknown lexicon
uncertain*	227,014	(10.57‱)	191	(12.87‱)
unknown	525,536	(24.48‱)	499	(33.62‱)
Hedging lexicon
maybe	10,286	(0.48‱)	142	(9.57‱)
may	5,946,955	(276.96‱)	10,050	(677.19‱)
might	949,536	(44.22‱)	2,639	(177.82‱)
possible	1,751,994	(81.59‱)	1,611	(108.55‱)
potential	2,879,336	(134.10‱)	2,675	(180.25‱)
seems	333,677	(15.54‱)	154	(10.38‱)
perhaps	84,058	(3.91‱)	32	(2.16‱)
likely	1,052,986	(49.04‱)	1,248	(84.09‱)
sometimes	119,942	(5.59‱)	26	(1.75‱)
Conflicting lexicon
conflict*	175,516	(8.17‱)	59	(3.98‱)
contradict*	46,639	(2.17‱)	10	(0.67‱)
controvers*	208,264	(9.70‱)	308	(20.75‱)
debat*	122,332	(5.70‱)	54	(3.64‱)
no consensus	17,907	(0.83‱)	9	(0.61‱)
questionable*	21,159	(0.99‱)	5	(0.34‱)
refut*	9,710	(0.45‱)	9	(0.61‱)

#	PMID	Year	Sentence	Subject	Predicate	Object
1	11748351	2001	95232561. The high level of low-density lipoprotein (LDL) is a risk factor for cardiovascular disease.	Low-Density Lipoproteins	PREDISPOSES	Cardiovascular Diseases
1	11748351	2001		(Chem. & Drugs)	(others)	(Disorders)
2	16541193	2006	62140. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following irbesartan treatment in Chinese hypertensive patients	Hypertensive	PROCESS_OF	Patients
				(Disorders)	(functionally_related_to)	Living Beings
				Therapeutic procedure	USES	irbesartan
				Procedures	(functionally_related_to)	(Chem. & Drugs)
				irbesartan	TREATS	Patients
				(Chem. & Drugs)	(functionally_related_to)	Living Beings
				irbesartan	TREATS	Hypertensive
				(Chem. & Drugs)	(functionally_related_to)	(Disorders)
3	27733220	2016	7853995. Subgroup analysis for each outcome measure was performed for the observing time point after the transplantation of MSCs.	Stem cells	PART_OF	Marrow
3	27733220	2016		Anatomy	physically_related_to	Anatomy
4	32421381	2020	345332630. Our data seem to suggest that COVID-19 is probably an additional risk factor for DVT in hospitalized patients.	COVID-19	PREDISPOSES	Deep Vein Thrombosis
4	32421381	2020		(Disorders)	others	Physiology
5	32493073	2020	345298871. COVID-19 presented with deep vein thrombosis: an unusual presentation.	COVID-19	COEXISTS_WITH	Deep Vein Thrombosis
5	32493073	2020		(Disorders)	others	Physiology
6	32351121	2020	345367243. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19.	Angiotensin converting enzyme 2	CAUSES	COVID-19
6	32351121	2020		(Chem. & Drugs)	(functionally_related_to)	(Disorders)

#	Subject_Object Pair			Start year	End year	# Sentence	IE
1	Polymorphism, Genetic (Genetic Function / Physiology)	_	Coronary Arteriosclerosis (Disease or Syndrome / Disorders)	2010	2019	9	1.837
2	Fibrinogen (AAPP / Chem. & Drugs)	_	Ischemic stroke (Disease or Syndrome / Disorders)	2006	2015	5	1.522
3	Vascular Diseases (Disease or Syndrome / Disorders)	_	Human (Human / Living Beings)	2003	2013	4	1.500
4	Epinephrine (Hormone / Chem. & Drugs)	_	Cardiopulmonary Arrest (Pathologic Function / Disorders)	2007	2007	4	1.500
5	Ischemic stroke (Disease or Syndrome / Disorders)	_	Variation (Genetics) (NPOP / Phenomena)	2008	2016	4	1.500
6	Gene Expression (Genetic Function / Physiology)	_	Population Group (Human / Living Beings)	2016	2018	4	1.500
7	Reactive Oxygen Species (BACS / Chem. & Drugs)	_	Apoptosis (Cell Function / Physiology)	2017	2020	4	1.500
8	Basal Ganglia (BPOC / Anatomy)	_	Hematoma (Pathologic Function / Disorders)	2012	2017	4	1.500
9	HMG-CoA Reductase Inhibitors (Organic Chemical /Chem. & Drugs)	_	Acute coronary Syndrome (Disease or Syndrome / Disorders)	2009	2019	6	1.459
10	Hyperuricemia (Disease or Syndrome / Disorders)	_	Hypertensive Disease (Disease or Syndrome / Disorders)	2012	2019	14	1.430