I am working in the field of Precision Oncology, specializing on data mining. I have extensive experience with the entire range of clinical research, from basic science and all the way to clinical trials.
Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative ... more Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for i...
... Page 6. This book is dedicated to: Professor Tova Arzi (Emeritus Professor, Tel-Aviv Universi... more ... Page 6. This book is dedicated to: Professor Tova Arzi (Emeritus Professor, Tel-Aviv University, Israel), who was the senior editor's (JS) first teacher of plant anatomy and revealed to him many secrets of the Plant World, with all the best wishes for health and happiness. Page 7. ...
In bioinformatics, clinical data is rarely used. Here, we propose using bedsidedata in basic rese... more In bioinformatics, clinical data is rarely used. Here, we propose using bedsidedata in basic research, via bioinformatics methodologies. To demonstrate the potential of this so called Reverse Translational Bioinformatics approach, classical bioinformatics tools were applied to blood biomarker information attained from a large scale, open-access cross sectional survey. The results of this analysis include a novel classification of blood biomarkers, critical ages in which basic biological processes may shift in humans, and a possible approach to exploring the gender specificity of these shifts. Changes in normal values were also shown to be non-linear, with most of the non-linearity attributed to the shift from growth to maturity. Together, these finding demonstrate that reversed translational bioinformatics may contribute to basic research.
The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous D... more The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous Ds elements is largely unknown. Sequence analysis of native maize Ds elements indicates a complex chimeric structure formed through deletions of Ac sequences with or without insertions of Ac-unrelated sequence blocks. These blocks are often flanked by short stretches of reshuffled and duplicated Ac sequences. To better understand the mechanism leading to Ds formation, we designed an assay for detecting alterations in Ac using transgenic tobacco plants carrying a single copy of Ac. We found frequent de novo alterations in Ac which were excision rather than sequence dependent, occurring within Ac but not within an almost identical Ds element and not within a stable transposase-producing gene. The de novo DNA rearrangements consisted of internal deletions with breakpoints usually occurring at short repeats and, in some cases, of duplication of Ac sequences or insertion of Ac-unrelated fragme...
Journal of Child and Adolescent Psychopharmacology, 2013
Platelets (PLT), which serve as the primary hemostatic indicator, can be used as a peripheral mod... more Platelets (PLT), which serve as the primary hemostatic indicator, can be used as a peripheral model for studying monoamine turnover in the brain. Therefore, they are attractive targets as circulatory biomarkers for the detection of psychiatric disorders. However, PLT counts have not been utilized as a peripheral biomarker of psychopathology. This study was a retrospective analysis of PLT counts upon admission of 108drug-naïve adolescents hospitalized in an inpatient psychiatric department. PLT counts of patients with suicidal ideation (SI) were compared with those of nonsuicidal in patients (NSI) and those of 77 healthy adolescents, serving as a control group. The patients' disorders were diagnosed and classified by one of four American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM IV) diagnoses, that is, unipolar depression, bipolar depression, schizophrenia, and a pooled group of conduct and borderline personality disorders. Significantly higher PLT counts were observed in SI patients, as compared with NSI patients (300,200±53.3/mL vs. 253,900±53.2/mL, respectively; p=0.0001). A significant difference in PLT counts in SI patients, relative to the control group, was also noted (300,200±53.3/mL vs. 254,000±52/mL, respectively; p=<10(-26)). Finally, a significant difference in PLT counts was observed between conduct/borderline personality disorders patient with and without suicidal ideation (292,000±55/mL vs. 246,000±64/mL, respectively; p=0.001). PLT counts are higher in suicidal hospitalized adolescents than in nonsuicidal inpatients, as well as than in controls.
ABSTRACT A new server for interpreting microarray results, list to list (L2L), is described. This... more ABSTRACT A new server for interpreting microarray results, list to list (L2L), is described. This tool offers a unique approach to understand the meaning of microarray results, based on comparing them to previously identified lists of differentially expressed genes. The usefulness of the server is demonstrated by studying differential expression in primary tumours versus metastases in colon cancer.
Three tools for threshold-free enrichment analysis of microarray data are introduced: GSEA (gene ... more Three tools for threshold-free enrichment analysis of microarray data are introduced: GSEA (gene set enrichment analysis), ermineJ and DRIM (discovering rank imbalanced motifs). GSEA offers an interface to a specific algorithm and a well-defined pipeline for the identifying enrichment in diverse gene sets and the creation of signature profiles. ermineJ offers a combined front end to three different algorithms, two of which perform a cut-off-free enrichment analysis. DRIM comprises an implementation of a new algorithm and is specifically designed for the search of new transcription-factor-binding sites based on expression patterns. Together, these tools demonstrate an emerging trend in high-throughput data analysis-the joint analysis of raw results with external knowledge.
Age is an important factor when considering phenotypic changes in health and disease. Currently, ... more Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.
The maize transposon Activator (Ac) was the first mobile DNA element to be discovered. Since then... more The maize transposon Activator (Ac) was the first mobile DNA element to be discovered. Since then, other elements were found that share similarity to Ac, suggesting that it belongs to a transposon superfamily named hAT after hobo from Drosophila, Ac from maize, and Tam3 from snapdragon. We addressed the structure and evolution of hAT elements by developing new tools for
Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies ... more Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted...
Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative ... more Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for i...
... Page 6. This book is dedicated to: Professor Tova Arzi (Emeritus Professor, Tel-Aviv Universi... more ... Page 6. This book is dedicated to: Professor Tova Arzi (Emeritus Professor, Tel-Aviv University, Israel), who was the senior editor's (JS) first teacher of plant anatomy and revealed to him many secrets of the Plant World, with all the best wishes for health and happiness. Page 7. ...
In bioinformatics, clinical data is rarely used. Here, we propose using bedsidedata in basic rese... more In bioinformatics, clinical data is rarely used. Here, we propose using bedsidedata in basic research, via bioinformatics methodologies. To demonstrate the potential of this so called Reverse Translational Bioinformatics approach, classical bioinformatics tools were applied to blood biomarker information attained from a large scale, open-access cross sectional survey. The results of this analysis include a novel classification of blood biomarkers, critical ages in which basic biological processes may shift in humans, and a possible approach to exploring the gender specificity of these shifts. Changes in normal values were also shown to be non-linear, with most of the non-linearity attributed to the shift from growth to maturity. Together, these finding demonstrate that reversed translational bioinformatics may contribute to basic research.
The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous D... more The mechanism by which the maize autonomous Ac transposable element gives rise to nonautonomous Ds elements is largely unknown. Sequence analysis of native maize Ds elements indicates a complex chimeric structure formed through deletions of Ac sequences with or without insertions of Ac-unrelated sequence blocks. These blocks are often flanked by short stretches of reshuffled and duplicated Ac sequences. To better understand the mechanism leading to Ds formation, we designed an assay for detecting alterations in Ac using transgenic tobacco plants carrying a single copy of Ac. We found frequent de novo alterations in Ac which were excision rather than sequence dependent, occurring within Ac but not within an almost identical Ds element and not within a stable transposase-producing gene. The de novo DNA rearrangements consisted of internal deletions with breakpoints usually occurring at short repeats and, in some cases, of duplication of Ac sequences or insertion of Ac-unrelated fragme...
Journal of Child and Adolescent Psychopharmacology, 2013
Platelets (PLT), which serve as the primary hemostatic indicator, can be used as a peripheral mod... more Platelets (PLT), which serve as the primary hemostatic indicator, can be used as a peripheral model for studying monoamine turnover in the brain. Therefore, they are attractive targets as circulatory biomarkers for the detection of psychiatric disorders. However, PLT counts have not been utilized as a peripheral biomarker of psychopathology. This study was a retrospective analysis of PLT counts upon admission of 108drug-naïve adolescents hospitalized in an inpatient psychiatric department. PLT counts of patients with suicidal ideation (SI) were compared with those of nonsuicidal in patients (NSI) and those of 77 healthy adolescents, serving as a control group. The patients' disorders were diagnosed and classified by one of four American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM IV) diagnoses, that is, unipolar depression, bipolar depression, schizophrenia, and a pooled group of conduct and borderline personality disorders. Significantly higher PLT counts were observed in SI patients, as compared with NSI patients (300,200±53.3/mL vs. 253,900±53.2/mL, respectively; p=0.0001). A significant difference in PLT counts in SI patients, relative to the control group, was also noted (300,200±53.3/mL vs. 254,000±52/mL, respectively; p=<10(-26)). Finally, a significant difference in PLT counts was observed between conduct/borderline personality disorders patient with and without suicidal ideation (292,000±55/mL vs. 246,000±64/mL, respectively; p=0.001). PLT counts are higher in suicidal hospitalized adolescents than in nonsuicidal inpatients, as well as than in controls.
ABSTRACT A new server for interpreting microarray results, list to list (L2L), is described. This... more ABSTRACT A new server for interpreting microarray results, list to list (L2L), is described. This tool offers a unique approach to understand the meaning of microarray results, based on comparing them to previously identified lists of differentially expressed genes. The usefulness of the server is demonstrated by studying differential expression in primary tumours versus metastases in colon cancer.
Three tools for threshold-free enrichment analysis of microarray data are introduced: GSEA (gene ... more Three tools for threshold-free enrichment analysis of microarray data are introduced: GSEA (gene set enrichment analysis), ermineJ and DRIM (discovering rank imbalanced motifs). GSEA offers an interface to a specific algorithm and a well-defined pipeline for the identifying enrichment in diverse gene sets and the creation of signature profiles. ermineJ offers a combined front end to three different algorithms, two of which perform a cut-off-free enrichment analysis. DRIM comprises an implementation of a new algorithm and is specifically designed for the search of new transcription-factor-binding sites based on expression patterns. Together, these tools demonstrate an emerging trend in high-throughput data analysis-the joint analysis of raw results with external knowledge.
Age is an important factor when considering phenotypic changes in health and disease. Currently, ... more Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.
The maize transposon Activator (Ac) was the first mobile DNA element to be discovered. Since then... more The maize transposon Activator (Ac) was the first mobile DNA element to be discovered. Since then, other elements were found that share similarity to Ac, suggesting that it belongs to a transposon superfamily named hAT after hobo from Drosophila, Ac from maize, and Tam3 from snapdragon. We addressed the structure and evolution of hAT elements by developing new tools for
Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies ... more Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted...
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