Anand Kumar | Jindal Global Law School (original) (raw)

Papers by Anand Kumar

The Gene Ontology is an important tool for the representation and processing of information about... more The Gene Ontology is an important tool for the representation and processing of information about gene products and functions. It provides controlled vocabularies for the designations of cellular components, molecular functions, and biological processes used in the annotation of genes and gene products. These constitute three separate ontologies, of cellular components), molecular functions and biological processes, respectively. The question we address here is: how are the terms in these three separate ontologies related to each other? We use statistical methods and formal ontological principles as a first step towards finding answers to this question.

Drug Discovery Today: Biosilico, 2004

The automatic integration of information resources in the life sciences is one of the most challe... more The automatic integration of information resources in the life sciences is one of the most challenging goals facing biomedical informatics today. Controlled vocabularies have played an important role in realizing this goal,by making it possible to draw together information from heterogeneous sources secure in the knowledge that the same terms will also represent the same entities on all occasions of use. One of the most impressive achievements in this regard is the Gene Ontology (GO), which is rapidly acquiring the status of a de facto standard in the field of gene and gene product annotations, and whose methodology has been much intimated in attempts to develop controlled vocabularies for shared use in different domains of biology. The GO Consortium has recognized, however, that its controlled vocabulary as currently constituted is marked by several problematic features -features which are characteristic of much recent work in bioinformatics and which are destined to raise increasingly serious obstacles to the automatic integration of biomedical information in the future. Here, we survey some of these problematic features, focusing especially on issues of compositionality and syntactic regimentation. www.drugdiscoverytoday.com REVIEWS RESEARCH FOCUS

We present the details of a methodology for quality assurance in large medical terminologies and ... more We present the details of a methodology for quality assurance in large medical terminologies and describe three algorithms that can help terminology developers and users to identify potential mistakes. The methodology is based in part on linguistic criteria and in part on logical and ontological principles governing sound classifications. We conclude by outlining the results of applying the methodology in the form of a taxonomy different types of errors and potential errors detected in SNOMED-CT.

The integration of biomedical terminologies is indispensable to the process of information integr... more The integration of biomedical terminologies is indispensable to the process of information integration. When terminologies are linked merely through the alignment of their leaf terms, however, differences in context and ontological structure are ignored. Making use of the SNAP and SPAN ontologies, we show how three reference domain ontologies can be integrated at a higher level, through what we shall call the OBR framework (for: Ontology of Biomedical Reality). OBR is designed to facilitate inference across the boundaries of domain ontologies in anatomy, physiology and pathology.

Formal principles governing best practices in classification and definition have for too long bee... more Formal principles governing best practices in classification and definition have for too long been neglected in the construction of biomedical ontologies, in ways which have important negative consequences for data integration and ontology alignment. We argue that the use of such principles in ontology construction can serve as a valuable tool in error-detection and also in supporting reliable manual curation. We argue also that such principles are a prerequisite for the successful application of advanced data integration techniques such as ontology-based multi-database querying, automated ontology alignment and ontology-based text-mining. These theses are illustrated by means of a case study of the Gene Ontology, a project of increasing importance within the field of biomedical data integration.

Artificial Intelligence in Medicine, 2007

Formalisms based on one or other flavor of Description Logic (DL) are sometimes put forward as he... more Formalisms based on one or other flavor of Description Logic (DL) are sometimes put forward as helping to ensure that terminologies and controlled vocabularies comply with sound ontological principles. The objective of this paper is to study the degree to which one DLbased biomedical terminology (SNOMED CT) does indeed comply with such principles. We defined seven ontological principles (for example: each class must have at least one parent, each class must differ from its parent) and examined the properties of SNOMED CT classes with respect to these principles. Our major results are: 31% of these classes have a single child; 27% have multiple parents; 51% do not exhibit any differentiae between the description of the parent and that of the child. The applications of this study to quality assurance for ontologies are discussed and suggestions are made for dealing with the phenomenon of multiple inheritance. The advantages and limitations of our approach are also discussed.

We present two algorithms that can help terminology developers and users to identify potential ar... more We present two algorithms that can help terminology developers and users to identify potential areas of improvement. We demonstrate the methodology by applying the algorithms to one of the most popular terminologies, SNOMED-CT®. Analysis of the results provides evidence for the thesis that both formal logical and linguistic tools should be used in the development and quality-assurance process of large terminologies.

Relations in biomedical ontologies

To enhance the treatment of relations in biomedical ontolog... more Relations in biomedical ontologies

To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.

Current Opinion in Critical Care, 2002

The nature of myocardial dysfunction during sepsis and septic shock has been investigated for mor... more The nature of myocardial dysfunction during sepsis and septic shock has been investigated for more than half a century. This review traces the evolution of scientific thought regarding this phenomenon during this period with particular emphasis on the current understanding of both the clinical manifestations and the molecular/cellular basis of septic myocardial dysfunction in critically ill patients. Current data suggest, contrary to older literature, that patients with septic shock develop a hyperdynamic circulatory state after fluid resuscitation and maintain this hyperdynamic circulatory state until death or recovery. Overt myocardial depression, as manifested by decreased cardiac output, is decidedly uncommon, even in the preterminal phase. Nonetheless, myocardial depression, as evidenced by biventricular dilation and depression of the ejection fraction, can be demonstrated in most patients with septic shock by using either radionuclide cineangiography or echocardiography. Depression is reversible over the course of 7 to 10 days in survivors. Available evidence suggests that myocardial hypoperfusion is not responsible for septic myocardial depression, because examination of humans with septic shock demonstrates increased myocardial perfusion, and animal models of septic shock appear to maintain myocardial high-energy phosphates. A circulating factor or factors, including the cytokines tumor necrosis factor alpha and interleukin-1beta, appear to have a significant role in the phenomenon. In addition, septic myocardial depression appears to be mediated in part through combinations of nitric oxide-dependent and -independent alterations of basal and catecholamine-stimulated cardiac myocyte contractility.

Critical Care Medicine, 2004

T he thermodilution-capable, balloon-tipped pulmonary artery catheter (PAC) has been a mainstay i... more T he thermodilution-capable, balloon-tipped pulmonary artery catheter (PAC) has been a mainstay in the management of the hemodynamically unstable patient in the intensive care unit for the last 30 yrs. In recent years, the therapeutic utility of the PAC has been challenged based on studies suggesting an unfavorable balance of risk and benefit. Sandham et al.

Previous studies have demonstrated the presence of myocardial depression in clinical and experime... more Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)ot and interleukin (IL)113, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-0c and IL-113 each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-cx and IL-1[3 induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-cx and IL-113 (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon ~/failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-0t and IL-113 cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.

Critical Care Medicine, 2006

Objective: To determine the prevalence and impact on mortality of delays in initiation of effecti... more Objective: To determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock.

Critical Care Clinics, 2000

Myocardial depression is a major but poorly understood component of septic shock. This study inve... more Myocardial depression is a major but poorly understood component of septic shock. This study investigates the morphologic and biochemical abnormalities associated with septic shock. Myocardial cells are incubated in normal and septic plasma in a nutrient-, oxygen-, pH-, electrolyte-, and temperature-controlled environment. Cells and media are tested for basal- and epinephrine-stimulated cyclic adenosine monophosphate (cAMP), lactic dehydrogenase (LDH), and creatine kinase. Electron microscopic studies are done at the end of incubation. Septic LDH and creatine kinase levels in the media are increased substantially, and septic cAMP levels are reduced significantly. Septic cells beat irregularly and arrest along with exhibiting abnormal electron microscopic structure. Septic myocardial dysfunction occurs independently of previously postulated causes that are controlled for in this experiment and therefore may be due to endogenously produced or accumulated toxic factor(s).

Critical Care, 2002

500 CI = cardiac index; cNOS = constitutive nitric oxide synthase; CO = cardiac output; CVP = cen... more 500 CI = cardiac index; cNOS = constitutive nitric oxide synthase; CO = cardiac output; CVP = central venous pressure; IL = interleukin; iNOS = inducible nitric oxide synthase; LVEDVI = left ventricular end-diastolic volume index; LVEF = left ventricular ejection fraction; MDS = myocardial depressant substance; NO = nitric oxide; PAC = pulmonary artery catheter; PAWP = pulmonary artery wedge pressure; RVEF = right ventricular ejection fraction; SVR = systemic vascular resistance; TNF-α = tumor necrosis factor alpha.