The characteristics of holistic, dynamics, complexity, and spatial and temporal features enable “Omics” and theories of TCM to interlink with each other. HPO, namely, “characterization,” can be understood as a sorting and generalization of the manifestations shown by people with diseases on the basis of the phenomics. Syndrome is the overall “manifestation” of human body pathological and physiological changes expressed by four diagnostic methods’ information. The four diagnostic methods’ data could be the most objective and direct manifestations of human body under morbid conditions. In this aspect, it is consistent with the connation of “characterization.” Meanwhile, the four diagnostic methods’ data also equip us with features of characterization in HPO. In our study, we compared 107 pieces of four diagnostic methods’ information with the “characterization database” to further analyze data of four diagnostic methods’ characterization in accordance with the common characteristics of four diagnostic methods’ information and characterization and integrated 107 pieces of four diagnostic methods’ data to relevant items in HPO and finished the expansion of characterization information in HPO.
Since the early 1990s, “omics” began to emerge in the field of life sciences as the most compelling concept, including genomics, proteomics, transcriptomics, and metabolomics. The characteristics of holistic, dynamics, complexity, and spatial and temporal features enable “omics” and theories of TCM to interlink with each other. The holistic and systematic ideology of TCM is reflected at a macro level, while the omics technology is the reintegration based on comprehensive analysis and restoration. Omics technology helps to quantify, objectify, and standardize TCM theory and further provides a new platform to evidence-based researches on TCM theories.
With the rise and development of different types of “omics,” in 1996, Steven A. Garan, Director of Aging Research Center, first put forward the concept of “phenomics” in a lecture delivered at the University of Waterloo. Phenome refers to all the phenotypes of a cell or an organism, whose life activities are reflected through phenotypes. Phenomics is a subject studying all phenotypes of an organism or a cell in various conditions at the genomic level [
The HPO was initially developed using information from OMIM, which is an important data resource in the field of human genetics and beyond. HPO is being developed in an effort to provide a standardized, controlled vocabulary that allows phenotypic information to be described in an unambiguous fashion in medical publications and databases. The HPO is currently using information from OMIM and medical literature. It contains approximately 10,000 terms and over 50,000 annotations to hereditary diseases are available for download. Terms in HPO describe a phenotypic abnormality, such as atrial septal defect. The HPO aims to provide a standardized vocabulary of phenotypic abnormalities encountered in human disease [
Phenotype is not only the combination of all the phenomena and features which are manifested; but it also can reflect the essence or nature of things by some means or information. Characterization is widely used in various disciplines. Wright and his team came up with Human Face Recognition Model based on sparse characterizations [
TCM follows the basic principle of pattern identification and syndrome differentiation in its clinical practice and believes that accurate differentiation of syndromes is a prerequisite for effective treatment. The called “treatment based on syndrome differentiation” is the basic principle to recognize and treat the disease, and a kind of special researching and treating method for disease in traditional Chinese medicine, including two processes of syndrome differentiation and treatment. TCM syndrome is a kind of pathological generalization of the disease at a certain stage during its development. Because TCM syndrome includes the ill issues, causes, property and the relationship between healthy energy and evil struggle, reflecting the essence of pathological changes of disease development at certain stages, so it could reveal the nature of the disease more comprehensive than simple symptoms. Four diagnostic methods’ information included inspection, listening and smelling, interrogation, and pulse feeling and palpation. Syndrome is the overall “manifestation” of human body pathological and physiological changes which can be expressed by four diagnostic methods’ information; for example, tongue picture is not only the most important indicator of symptoms and disease patterns of human body, but also the external manifestation of overall body conditions [
We selected 385 CHD cases with UAP admitted by Dongzhimen Hospital, which is the affiliated hospital of Beijing University of Chinese Medicine, China-Japan Friendship Hospital, Beijing Anzhen Hospital, Zhengzhou Hospital of Traditional Chinese Medicine, Wuhan Hospital of Traditional Chinese Medicine, and Hubei Hospital of Traditional Chinese Medicine, from May 2009 to March 2011.
Other 1665 cases in the follow-up study were selected from patients with CHD and UAP hospitalizing from September 2008 to March 2011, in Dongzhimen Affiliated Hospital of Beijing University of Chinese Medicine, East Hospital, Ministry of Health directly supervised China-Japan Friendship Hospital, Wuhan Hospital of Chinese Medicine, Hospital of Zhengzhou City, Hubei Hospital of Traditional Chinese Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, Hangzhou Hospital of Traditional Chinese Medicine, Chengdu Hospital of Traditional Chinese Medicine and Western Medicine, Affiliated Hospital of Inner Mongolia Medical College, Yichang Hospital of Traditional Chinese Medicine, Henan Hospital of Traditional Chinese Medicine, Wuxi Hospital of Traditional Chinese Medicine, Zibo Hospital of Traditional Chinese Medicine, and Cardiology Department of Changzhou Hospital of Traditional Chinese Medicine.
The diagnostic criteria of angina pectoris was referred to the Treatment Guidelines Chronic Stable Angina (1999) jointly identified by American College of Cardiology (ACC)/American Heart Association (AHA)/American College of Physicians and the American Society of Internal Medicine ACP-ASIM [
The TCM clinical diagnosis criteria of angina pectoris was referred to chapter of syndrome and pattern in
General information, history of present illness, past history, personal illness, family disease history, and other related symptoms of patients meeting the inclusion criteria with UAP and CHD were gathered within 24 hours of admission to make a detailed record of four diagnostic methods’ information data and complete the four clinical diagnostic information collection forms. The collection of four diagnostic methods’ extended phenotypes served as indicators of the above five TCM patterns information and patients’ disease history must be done by professionals, who must meet with at least one of the following specific requirements: physicians with professional qualification; attending physician or above; and personnel with two years of relevant clinical experience or more; postgraduate students of relevant majors in their first year or above can only participate under the supervision of attending physicians or above.
Within 24 hours of admission, three deputy chief physicians with 5 years or more of clinical experience in relevant field would give judgments on TCM syndromes/syndrome factors (the complex TCM syndrome is decomposed into more limited elements, with more relatively clear content, which is called the TCM “syndrome elements”) and syndrome identification based on previous diagnosis of patients. Identification criteria of syndrome/syndrome factors are as follows: (1) identification can be made when the three physicians hold the same opinion; (2) when one physician disagrees with the other two, the opinion of the latter two would be adopted; (3) when the 3 physicians hold different opinions against each other, the deputy director or above can recollect information obtained by the four diagnostic methods’ information and identify syndrome, syndrome factors, and disease pattern all over again until it meets with the first and second situation.
Tongue pictures of 212 patients were taken by a digital camera (RICOH, R10, 10 million pixels) after 10:00 a.m. before lunch. Before shooting, patients would rise 2 to 3 times with warm water and have a 15-minute rest. When pictures were taken under natural light, patients would keep in a sitting position against the light and roll their tongue to the largest extent to expose their sublingual collaterals (there are two longitudinal veins on each side of the frenum linguae under the tongue, which is called “sublingual collaterals” in TCM).
The camera would be backlit during shooting, turning off the flash while using colorimetric cards. The color cards were close to the patients’ tongue and maintained the same level with tongue. The camera and color card were kept in a vertical position. The focal point lied in the junction of the tongue and the colorimetric cards. Photos of tongue picture included visible color cards and full view of sublingual collaterals. The time limit of patients sticking out their tongue should not exceed 15 seconds every time. Shooting of tongue pictures would resume after a 5-minute break. There must be no less than three clear pictures of sublingual collaterals for each patient.
Observation measures of sublingual collaterals can refer to the formulation that sublingual collaterals can be described from the following four aspects: length, thickness, tortuosity, and color in
107 pieces of four diagnostic methods’ information gathered from clinical epidemiological surveys on the UAP patients mentioned above were used as data sources, including chest pain, chest distress, short breath, palpitation, cough, aversion to cold and cold extremities, fatigue and weakness, spontaneous perspiration, night sweat, burning sensation of five centers, eyestrain, dry mouth, dizziness, amnesia, fainting feeling, tinnitus, dry and hot face, insomnia, irascibility, hypochondrium distending pain, sighing, depression, anorexia, abdominal distension, epigastric fullness, belching, nausea and vomiting, loose stool, constipation, sore lumbus and knees, frequency of micturition at night, limb numbness, heel pain, hemiplegia, subcutaneous ecchymosis, pachylosis, obesity, white phlegm, yellow phlegm, bloody phlegm, frothy sputum, pharyngeal foreign body sensation, thirst with no desire for drinks, tastelessness, bitter taste in the mouth, sweet taste in the mouth, salty taste in the mouth, viscous and greasy taste in the mouth, diarrhea, defecation asthenia, yellow urine and oliguria, clear urine in large amounts, residual urine, cold abdomen and waist, heavy limbs, pallor, bright pale complexion, darkish complexion, sallow complexion, red complexion, conjunctiva congestion, dark color around eyes, edema of the eyelids, dark red lip and gingival, pale lips and finger nails, dark color in palatal mucosa, lower abdominal tenderness, lower extremity edema, faint low voice, emaciation, pale tongue, red tongue, scarlet tongue, dark red tongue, dark purple tongue, swollen tongue body, thin tongue body, tooth-marked tongue, thick tongue coating, greasy tongue coating, curry tongue coating, scanty tongue coating, exfoliative tongue coating, no tongue coating, thick and greasy tongue coating, smooth tongue coating, yellow tongue coating, black tongue coating, glossal petechia, lavender subglossal collateral vessels, blue purple subglossal collateral vessels, black purple subglossal collateral vessels, mauve subglossal collateral vessels, faint red subglossal collateral vessels, subglossal collateral vessels engorgement, thin subglossal collateral vessels, deep pulse, rapid pulse, moderate pulse, knotted and intermittent pulse, slow pulse, thread pulse, wiry pulse, tense pulse, uneven pulse, smooth pulse, and weak pulse.
10-fold cross-validation method was applied to verify the decision tree model of recognition mode. TP represented the identification of the correct number of samples with blood stasis pattern; TF represented the correct recognition of number of samples without blood stasis pattern; FN meant the false identification of the number of samples with blood stasis pattern; FP meant misidentification of samples without blood stasis pattern [
Short, thin sublingual collaterals with mild and moderate tortuosity, showing a color of mild purple, could be seen in patients with pattern of congealing cold in heart vessel and pattern of phlegm obstruction in heart vessel; long, thick sublingual collaterals with medium or severe tortuosity, manifesting a color of dark purple or black purple, could be seen in patients with pattern of blood stagnation and pattern of blood obstruction in heart vessel; short, medium thin sublingual collaterals with mild tortuosity, exhibiting a color of mild purple, could be seen in patients with deficiency pattern, such as pattern of mutual deficiency of yin and qi, pattern of heart qi deficiency, heart yang deficiency pattern, and heart yin deficiency pattern. The results were shown in Table
The distribution of sublingual collaterals of patients with CHD with different patterns (example).
Patterns | Length of collaterals | Thickness of collaterals | Tortuosity of collaterals | Colors of collaterals | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Long | Medium | Short | Thick | Medium thick | Fine | Mild | Moderate | Severe | Mild purple | Dark | Black | |
Pattern of congealing cold in heart vessel | 0 | 0 | 4 | 0 | 0 | 4 | 4 | 0 | 0 | 4 | 0 | 0 |
Pattern of qi deficiency and blood stasis | 11 | 17 | 9 | 19 | 11 | 7 | 13 | 7 | 17 | 14 | 15 | 8 |
Pattern of mutual deficiency of qi and yin | 6 | 9 | 6 | 7 | 5 | 9 | 12 | 2 | 7 | 15 | 3 | 3 |
Pattern of qi stagnation and blood stasis | 4 | 8 | 0 | 6 | 4 | 2 | 5 | 2 | 5 | 5 | 4 | 3 |
Pattern of mutual obstruction of phlegm and qi | 10 | 6 | 4 | 9 | 5 | 6 | 10 | 4 | 6 | 9 | 4 | 7 |
Pattern of heart vessel phlegm obstruction | 1 | 2 | 7 | 1 | 3 | 6 | 10 | 0 | 0 | 8 | 2 | 0 |
Pattern of intense heart fire | 0 | 3 | 0 | 2 | 0 | 1 | 3 | 0 | 0 | 3 | 0 | 0 |
Pattern of heart vessel qi stagnation | 1 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | 0 | 1 | 1 | 0 |
Pattern of heart qi deficiency | 4 | 7 | 10 | 4 | 7 | 10 | 18 | 3 | 0 | 20 | 1 | 0 |
Heart blood stagnation pattern | 26 | 25 | 12 | 34 | 12 | 17 | 32 | 11 | 20 | 26 | 26 | 11 |
Heart yang deficiency pattern | 4 | 7 | 4 | 3 | 5 | 7 | 10 | 5 | 0 | 12 | 3 | 0 |
Heart yin deficiency pattern | 1 | 0 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 2 | 0 | 0 |
Mutual deficiency of heart yin and yang | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 1 |
Pictures of tongue surface and sublingual collaterals gathered from patients with UAP.
Variables and corresponding values selected by
Selected variables and corresponding values.
Selected variables |
|
Values | Eligible variables |
|
Values |
---|---|---|---|---|---|
Collateral color | 0.000 | 1, 2, 3 | Dark complexion | 0.000 | 0, 1 |
Cyanotic lips | 0.000 | 0, 1, 2, 3 | 0.5–1 cm dermal ecchymosis | 0.001 | 0, 1 |
Cyanotic hands and fingernails | 0.000 | 0, 1, 2, 3 | Ecchymosis along tongue sides | 0.001 | 0, 1 |
Collateral tortuosity | 0.000 | 0, 1, 2, 3 | Pale lips and fingernails | 0.002 | 0, 1 |
Dark blue tongue | 0.000 | 0, 1 | Ecchymosis | 0.002 | 0, 1 |
Dark red lips and gingival | 0.000 | 0, 1 | Tendency to be irritable and impatient | 0.002 | 0, 1 |
Thickness of collaterals | 0.000 | 1, 2, 3 | Fatigue | 0.003 | 0, 1, 2, 3 |
Length of collaterals | 0.000 | 1, 2, 3 | Laziness to speak due to qi deficiency | 0.003 | 0, 1, 2, 3 |
Dark and pale complexion | 0.000 | 0, 1 | Less than 3 ecchymosis cases | 0.003 | 0, 1 |
Dark Jaw mucosa | 0.000 | 0, 1 | Fissured tongue | 0.003 | 0, 1 |
Shadow circled eyes | 0.000 | 0, 1, 2, 3 | Tough tongue | 0.003 | 0, 1 |
Slippery pulse | 0.000 | 0, 1 | Tastelessness | 0.004 | 0, 1, 2, 3 |
Loss of appetite | 0.000 | 0, 1, 2, 3 | Hesitant pulse | 0.006 | 0, 1 |
Floating pulse | 0.000 | 0, 1 | Pale and dark complexion | 0.007 | 0, 1 |
Soft tongue | 0.000 | 0, 1 | Subcutaneous ecchymosis | 0.010 | 0, 1, 2, 3 |
10-fold cross-validation of decision tree model of blood stasis pattern for 411 cases of UAP.
Algorithm | TN | FP | Sensitivity (%) | Specificity (%) | Accuracy (%) |
---|---|---|---|---|---|
FN | TP | ||||
C4.5 | 123 | 46 | 77.7 | 72.8 | 75.7 |
54 | 188 | ||||
|
|||||
ADTree | 128 | 41 | 75.6 | 75.7 | 75.7 |
59 | 183 | ||||
|
|||||
CHAID | 132 | 37 | 70.7 | 78.1 | 73.7 |
71 | 171 | ||||
|
|||||
QUEST | 60 | 109 | 93.4 | 35.5 | 69.6 |
16 | 226 |
Decision tree model of blood stasis pattern identification for 411 cases of UAP. (a) C4.5 decision tree model; (b) ADTree decision tree model; (c) CHAID decision tree model; (d) QUEST decision tree model.
Compared with the characterization database, 23 of 107 pieces of four diagnostic methods’ information were consistent with it, namely, chest pain, heart palpitations, chills, fatigue, aversion to cold and cold limbs, spontaneous perspiration, night sweats, dysphoria in chest, palms and soles, dry eyes and mouth, dizziness, irritability and impatience, lack of tongue moss, depression, loss of appetite, bloating, nausea and vomiting, loose stools, nocturia, numbness, bruising, eyelid edema, lower limb edema, and tinnitus (see Table
Characterization reference form of 23 four diagnostic methods’ information.
Four diagnostic methods’ information | Characterizations | Item number |
---|---|---|
Palpitation | Palpitations | 7280 |
Aversion to cold and cold extremities | Asthenic habitus | 1852 |
Chest pain | Chest pain | 2588 |
Fatigue and weakness | Generalized weakness of limb muscles | 4583 |
Apneic episodes precipitated by illness, fatigue, stress | 1796 | |
Spontaneous perspiration | Hyperhidrosis | 4890 |
Night sweat | Hyperhidrosis | 4890 |
Burning sensation of five centers | Polydipsia | 7753 |
Eyestrain | Abnormal, jerky eye movements | 193 |
Dry mouth | Xerostomia | 10302 |
Dizziness | Paroxysmal vertigo | 7341 |
Vertigo | 10146 | |
Irascibility | Irritability | 5701 |
Scanty tongue coating | Smooth tongue | 9147 |
Depression | Depression | 3473 |
Anorexia | Anorexia | 1445 |
Abdominal distension | Abdominal distention | 71 |
Nausea and vomiting | Nausea | 6834 |
Nausea and vomiting | 6835 | |
Loose stool | Diarrhea | 3530 |
Frequency of micturition at night | Nocturia | 6961 |
Limb numbness | Cataplexy, paroxysmal weakness, or paralysis | 2467 |
Subcutaneous ecchymosis | Ecchymoses | 3790 |
Petechiae | 7646 | |
Edema of the eyelids | Periorbital edema | 7578 |
Lower extremity edema | Edema of the lower limbs | 3820 |
Tinnitus | Tinnitus | 9740 |
Hierarchical clustering is commonly used for unsupervised clustering. Agglomerative hierarchical clustering begins with each sample as separate cluster and then proceeds to combine them until all samples belong to one cluster. The result is usually presented as a dendrogram or a heat map. Cluster analysis showed that 21 of the above 23 four diagnostic methods’ information had automatically entered the cluster analysis, with the exclusion of “chest pain” and “less moss.” 21 four diagnostic methods’ information were aggregated into five parts and the polymerization was good. These five parts prompted five kinds of Chinese medicine syndrome/syndrome elements, respectively, after analysis: spontaneous sweating, nausea, vomiting, bloating, loss of appetite, dizziness, palpitations, and lassitude, all of which aggregated into “qi deficiency” pattern; numbness and subcutaneous stasis blood aggregated into “blood stasis” syndrome pattern; depression, irritability, and impatience aggregated into “qi stagnation” pattern; nocturia, chills, loose stools, eyelid edema, and lower limb edema aggregated into “yang deficiency” pattern; dry eyes, tinnitus, night sweats, dysphoria in chest, palms and soles, and dry mouth aggregated into pattern of “yin deficiency” (see Figure
Cluster analyses of 23 characterizations. (a) Data standardization chart; (b) cluster analysis heat map; ZH = spontaneous, EXOT = nausea, vomiting, FZ = bloating, SYBZ = loss of appetite, TY = dizziness, XJ = palpitations, JDFL = lassitude, ZTMM = numbness, PXYX = subcutaneous bleeding, YY = depression, JZYN = irritability, YNPD = nocturia, WHZL = chills and cold limbs, BT = loose stools, YJFZ = eyelid edema, XZSZ = lower extremity edema, LMGS = dry eyes, EM = tinnitus, DH = night sweats, WXFR = dysphoria in chest, palms and soles, and KG = dry mouth.
Based on the identification of five TCM patterns, we expanded the sample volume to 2,050 and extended the phenotypes from 21 to 107. We did a complex network analysis on these 107 pieces of information. The results showed that the center of complex network node classification chart was composed of 21 pieces of four diagnostic methods’ information, which were consistent with the characterization database, and different colors were assigned to represent five kinds of patterns, namely, pattern of qi deficiency, of blood stasis, of qi stagnation, and of yin and yang deficiency. There were 71 pieces of extended phenotypes served as indicators for the above five TCM patterns, which were arranged in order of priority around the center of network. There were 15 more phenotypes which were not involved into complex network, including emaciation, pale tongue, and rapid pulse, and their information node was 0.
The results of characterization information network properties indicate that 36 characterizations node values are 17. The maximum occupation of a characterizing information in the figure means that it has the maximum contribution to the identification of the various syndromes. Connected component represents the similarities of each node in the phenotypes network, and it means that nodes with consistent connectivity numbers are in the same network. The network with connectivity number of 1 is more complex, including 69 phenotypic nodes (Table
Indicators of 107 characterization properties of complex networks.
Phenotypes | Values | Connected component values |
---|---|---|
Chest pain | 3 | 1 |
Chest distress | 17 | 1 |
Short breath | 17 | 1 |
Palpitation | 17 | 1 |
Cough | 17 | 1 |
Aversion to cold and cold extremities | 1 | 1 |
Fatigue and weakness | 17 | 1 |
Spontaneous perspiration | 17 | 1 |
Night sweat | 2 | 1 |
Burning sensation of five centers | 2 | 1 |
Eyestrain | 2 | 1 |
Dry mouth | 2 | 1 |
Dizziness | 17 | 1 |
Amnesia | 2 | 1 |
Fainting feeling | 17 | 1 |
Tinnitus | 2 | 1 |
Dry and hot face | 2 | 1 |
Insomnia | 17 | 1 |
Irascibility | 4 | 1 |
Hypochondrium distending pain | 4 | 1 |
Sighing | 4 | 1 |
Depression | 4 | 1 |
Anorexia | 17 | 1 |
Abdominal distension | 17 | 1 |
Epigastric fullness | 17 | 1 |
Belching | 17 | 1 |
Nausea and vomiting | 17 | 1 |
Loose stool | 1 | 2 |
Constipation | 1 | 3 |
Sore lumbus and knees | 1 | 1 |
Frequency of micturition at night | 1 | 1 |
Limb numbness | 3 | 1 |
Heel pain | 1 | 4 |
Hemiplegia | 3 | 2 |
Subcutaneous ecchymosis | 3 | 2 |
Pachylosis | 3 | 2 |
Obesity | 17 | 1 |
White phlegm | 17 | 1 |
Yellow phlegm | 17 | 1 |
Bloody phlegm | 1 | 5 |
Frothy sputum | 17 | 1 |
Pharyngeal foreign body sensation | 1 | 6 |
Thirst with no desire for drinks | 3 | 2 |
Tastelessness | 17 | 1 |
Bitter taste in the mouth | 2 | 1 |
Sweet taste in the mouth | 17 | 1 |
Salty taste in the mouth | 3 | 1 |
Viscous and greasy taste in the mouth | 17 | 1 |
Diarrhoea | 1 | 7 |
Defecation asthenia | 1 | 8 |
Yellow urine and oliguria | 4 | 1 |
Clear urine in large amounts | 1 | 1 |
Residual urine | 1 | 1 |
Cold abdomen and waist | 1 | 1 |
Heavy limbs | 17 | 1 |
Pallor | 1 | 1 |
Bright pale complexion | 1 | 9 |
Darkish complexion | 3 | 1 |
Sallow complexion | 1 | 10 |
Red complexion | 1 | 11 |
Conjunctival congestion | 1 | 12 |
Dark color around eyes | 3 | 1 |
Edema of the eyelids | 1 | 1 |
Dark red lip and gingiva | 3 | 1 |
Pale lips and finger nails | 17 | 1 |
Dark color in palatal mucosa | 3 | 1 |
Lower abdominal tenderness | 3 | 1 |
Lower extremity edema | 1 | 1 |
Faint low voice | 17 | 1 |
Emaciation | 0 | 13 |
Pale tongue | 0 | 14 |
Red tongue | 0 | 15 |
Scarlet tongue | 0 | 16 |
Dark red tongue | 8 | 1 |
Dark purple tongue | 3 | 1 |
Swollen tongue body | 0 | 17 |
Thin tongue body | 0 | 18 |
Tooth-marked tongue | 17 | 1 |
Thick tongue coating | 17 | 1 |
Greasy tongue coating | 17 | 1 |
Curdy tongue coating | 0 | 19 |
Scanty tongue coating | 0 | 20 |
Exfoliative tongue coating | 0 | 21 |
No tongue coating | 0 | 22 |
Thick and greasy tongue coating | 17 | 1 |
Smooth tongue coating | 17 | 1 |
Yellow tongue coating | 8 | 1 |
Black tongue coating | 0 | 23 |
Glossal petechia | 3 | 1 |
Lavender subglossal collateral vessels | 3 | 1 |
Blue purple subglossal collateral vessels | 3 | 1 |
Black purple subglossal collateral vessels | 0 | 24 |
Mauve subglossal collateral vessels | 0 | 25 |
Faint red subglossal collateral vessels | 17 | 1 |
Subglossal collateral vessels engorgement | 3 | 1 |
Thin subglossal collateral vessels | 17 | 1 |
Deep pulse | 17 | 26 |
Rapid pulse | 0 | 27 |
Moderate pulse | 17 | 28 |
Knotted and intermittent pulse | 0 | 29 |
Slow pulse | 1 | 29 |
Thready pulse | 17 | 26 |
Wiry pulse | 4 | 26 |
Tense pulse | 1 | 30 |
Uneven pulse | 1 | 31 |
Smooth pulse | 17 | 26 |
Weak pulse | 17 | 1 |
Complex characterization network node classification map of 2050 CHD patients with UAP.
After comparing with items in HPO, we classified the 107 four diagnostic methods’ information, following six principles. First, the appropriate characterizations were classified under the existing diseases or phenotype entries as a symptom, which took up the largest proportion of classification; for example, chest pain, chest distress, and short breath were classified under angina pectoris; cough, white phlegm, yellow phlegm, bloody phlegm, and frothy phlegm were classified under pneumonia; intolerance of cold and cold limb and burning sensation of five centers were classified under the abnormality of temperature regulation; hypodynamia and faint low voice were classified under the weakness of the classification. Second, phenotypes fully consistent with the HPO database entries could be directly classified, like palpitations, abdominal distension, depression, tinnitus, and petechiae. Third, a child node under the original entry was built, and then a lower sub-child node at next level was created under the child node, for example, establishing a child node of “abnormality of the waist” under “phenotypic abnormality”, and then creating a sub-child node of “sore waist and knee” under the “abnormality of the waist”; establishing a child node “abnormality of the perspiration” under the “abnormality of fluid regulation” and then building two sub-child nodes describing “spontaneous perspiration and night sweat” under it; Fourth, deeper descriptions for the original entries, for example, “cold sensation in abdomen” for further description about abnormality of the abdomen; “lower abdominal tenderness” made a detailed description of the location of abdominal pain; “epigastric fullness” was classified under the “abdominal distention”; bitter, sweet, salty, viscous, and greasy taste in the mouth made a detailed description of the “abnormality of taste sensation.” Fifth, items had similar meaning with original entries, for example, “irritable tantrum” and its original entry “aggressive behavior”; “sighing” and its original entry “depression”; “edema of the eyelids” and its original entry “palpebral edema”; “obesity” and its original entry “increased adipose tissue.” Sixth, description of tongue and pulse were added, in which there were 11 additional entries for pulse; 26 additional entries for tongue, and these entries were listed, respectively, in the classifications of tongue color abnormity, tongue morphological abnormalities, abnormal tongue moss, tongue ecchymosis petechiae, and abnormal sublingual collaterals.
Tongue diagnosis is an important part of TCM inspection with a long history. It has become a very unique diagnostic method for TCM nowadays. Tongue is the seedling of heart; heart opens at tongue; the tongue is the external manifestation of heart. It is recorded in Spiritual Pivot • Meridians that “The Collateral Hand Taiyin stems and runs upward and parallel to the Channel of Hand Shaoyin into the heart. It then runs upward to link the root of tongue and pertains to the eye system.” Spiritual Pivot • Maidu records that “Heart qi goes through the tongue, only when the heart is in harmony, the tongue can taste five flavors.” Sublingual collateral diagnostic method is convenient, accurate, and noninvasive. Therefore, a lot of clinical observations of reproducibility and timeliness can be made on patients [
We obtained four decision tree models of blood stasis syndrome diagnosis by extending tongue characterizations to 30 TCM four diagnostic methods’ information of statistical significance and exploring with data mining methods of decision tree model. Nowadays, in modern medicine, TCM four diagnostic methods’ information is seen as non-disease specific clinical manifestations and is of little significance in clinical diagnosis of Western medicine [
Furthermore, we expanded 30 pieces of four diagnostic methods’ information to 107 pieces. After comparing with the OMIM characterization database, there were 23 characterizations exactly consistent with each other. Results of cluster analysis showed that 21 of the 23, respectively, aggregated into five kinds of syndromes/syndrome elements and enabled the identification of qi deficiency pattern, blood stasis pattern, qi stagnation pattern, yin deficiency pattern, and yang deficiency pattern. In HPO, the use of an ontology to capture phenotypic information allows the use of computational algorithms that exploit semantic similarity between related phenotypic abnormalities to define phenotypic similarity metrics, which can be used to perform database searches for clinical diagnostics or as a basis for incorporating the human phenome into large-scale computational analysis of gene expression patterns and other cellular phenomena associated with human disease [
Next, we extended the sample volume of UAP cases from 385 cases to 2,050 cases, and with the application of complex network approach, we expanded 21 pieces of four diagnostic methods’ characterizations to 107 pieces. There were altogether 92 characterizations being involved as components of the complex network of recognition of qi deficiency pattern, blood stasis pattern, qi stagnation pattern, and yin and yang deficiency pattern. Complex system is a network system controlled by a few hubs, with a large number of functional groups composed by hubs. It can reflect some or all of its overall characteristics or characteristics in common [
The overall behavior of the system cannot be obtained only by the simple act of components (such as the functions or the features). Therefore, research methods and thinking of complex systems should be combined with when we study the syndromes and genes, proteins, and metabolomics. In addition, it should be understood that proper research ideas and research methods are usually the key points in syndrome studies. For example, a network balance model can evaluate the imbalanced network underlying TCM syndrome and find potential biomarkers [
After a series of reasoning, it can be believed that 107 pieces of four diagnostic methods’ information can be classified as the extended entry of characterization items in HPO, and the four diagnostic methods’ information of TCM is the constituent part of “phenomics.” A large-scale, standardized database of TCM four diagnostic methods’ information using the HPO research model can be formed and realize the “high throughput analysis” based on characteristic information and then achieve the promotion of “phenomics” on systems biology. The concept of phenomics proposed by this paper is actually an extension of the traditionally defined “omics,” which usually refers to genomics, proteomics, transcriptomics and metabolomics, and so forth. Although the genomics research status was not involved in this study, the characteristics, such as integrity, dynamics, temporality, spatiality and complexity shared by both TCM four diagnostic methods’ information and the concept of “omics” were firmly grasped by this research. HPO, based on phenomics, can be interpreted as a data-sorting and data-summarizing method for the symptoms displayed by human body in disease condition, which is in line with the connotation of the TCM four diagnostic methods’ information. There is no doubt that the diversity of genome leads to the complex phenotypes, on which aspect we will do further study in the future.
Traditional Chinese medicine
Human Phenotype Ontology
Online Mendelian Inheritance in Man
Coronary heart disease
Unstable angina pectoris
True positives
True false
False negatives
False positives.
The authors declare that they have no conflict of interests.
Qi Shi collected the clinical data, analyzed data, and generated figures and paper. Kuo Gao designed the project, project coordination, and major revision of paper. Huihui Zhao collected the clinical data and generated paper; Juan Wang designed the project and project coordination. Xing Zhai and Peng Lu revised the paper and methodology support; Jianxin Chen designed the project, analyzed data, and generated figures and paper. Wei Wang designed the project, project coordination, and generated paper. All authors have read and approved the final version of the paper. Qi Shi and Kuo Gao and Huihui Zhao contributed equally to this work.
This study was supported by the National Basic Research Program of China (no. 2011CB505106); National Science Foundation of China (nos. 81173463, 81102730, 81302914, 81473521, and 81303152); New Century Excellent Talent Support Plan of the Ministry of Education (NCET-12-084 and NCET-11-0607); Beijing Nova Program (Grant nos. xx2013032 and 2011069); Innovation Team of Wei Wang in Beijing University of Chinese Medicine; Project of Beijing Young Talents (YETP0821 by Xing Zhai); Special Project of Chinese Administration of Traditional Chinese Medicine (537/01204, 200807007 by Wei Wang).