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Article ; Online: Pharma's Bio-AI revolution.

Bentwich, Isaac

2023 Volume 28, Issue 5, Page(s) 103515

Abstract: Drug development has become unbearably slow and expensive. A key underlying problem is the clinical prediction challenge: the inability to predict which drug candidates will be safe in the human body and for whom. Recently, a dramatic regulatory change ... ...

Abstract	Drug development has become unbearably slow and expensive. A key underlying problem is the clinical prediction challenge: the inability to predict which drug candidates will be safe in the human body and for whom. Recently, a dramatic regulatory change has removed FDA's mandated reliance on antiquated, ineffective animal studies. A new frontier is an integration of several disruptive technologies [machine learning (ML), patient-on-chip, real-time sensing, and stem cells], which when integrated, have the potential to address this challenge, drastically cutting the time and cost of developing drugs, and tailoring them to individual patients.
MeSH term(s)	Animals ; Humans ; Artificial Intelligence ; Machine Learning ; Drug Development
Language	English
Publishing date	2023-02-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2023.103515
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Article: Identifying human microRNAs.

Bentwich, Isaac

Current topics in microbiology and immunology

2007 Volume 320, Page(s) 257–269

Abstract: MicroRNAs are a recently discovered group of short, non-coding RNA regulatory genes found in many species including humans. Originally viewed as a rare curiosity, over a thousand peer-reviewed publications have now established their major role in health ... ...

Abstract	MicroRNAs are a recently discovered group of short, non-coding RNA regulatory genes found in many species including humans. Originally viewed as a rare curiosity, over a thousand peer-reviewed publications have now established their major role in health and disease. MicroRNA discovery approaches, both biological and computational, have played an important role in this enfolding drama, and have led to the discovery of many hundreds of novel microRNAs. These different discovery and validation approaches are briefly reviewed here, as are the challenges and questions that lie ahead.
MeSH term(s)	Computational Biology ; Humans ; MicroRNAs/analysis ; MicroRNAs/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2007-11-06
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0070-217X
ISSN	0070-217X
DOI	10.1007/978-3-540-75157-1_12
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Article ; Online: A postulated role for microRNA in cellular differentiation.

Bentwich, Isaac

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2005 Volume 19, Issue 8, Page(s) 875–879

Abstract: Over the past two decades a variety of mechanisms regulating cellular differentiation have been uncovered. These include signaling by morphogens or membrane-associated ligands and asymmetric segregation of cytoplasmic components. Most of these processes ... ...

Abstract	Over the past two decades a variety of mechanisms regulating cellular differentiation have been uncovered. These include signaling by morphogens or membrane-associated ligands and asymmetric segregation of cytoplasmic components. Most of these processes are driven by protein coding genes. Here I describe another possible cellular differentiation mechanism that involves asymmetric segregation of microRNAs, a group of recently discovered non-protein coding genes that have been shown to be involved in differentiation.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; DNA Methylation ; MicroRNAs/genetics ; MicroRNAs/physiology ; Models, Biological ; Plants
Chemical Substances	MicroRNAs
Language	English
Publishing date	2005-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.04-3609hyp
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Article: Prediction and validation of microRNAs and their targets.

Bentwich, Isaac

FEBS letters

2005 Volume 579, Issue 26, Page(s) 5904–5910

Abstract: MicroRNAs are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs, and have been shown to play a central role in gene regulation in health and disease. Sophisticated computer-based prediction approaches of microRNAs ... ...

Abstract	MicroRNAs are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs, and have been shown to play a central role in gene regulation in health and disease. Sophisticated computer-based prediction approaches of microRNAs and of their targets, and effective biological validation techniques for validating these predictions, now play a central role in discovery of microRNAs and elucidating their functions.
MeSH term(s)	Algorithms ; Animals ; Artificial Intelligence ; Binding Sites ; Computational Biology ; Conserved Sequence ; Evolution, Molecular ; Humans ; MicroRNAs/chemistry ; MicroRNAs/physiology ; Microarray Analysis/methods ; Models, Biological ; Models, Genetic ; RNA/chemistry ; RNA Interference ; RNA Precursors ; RNA, Messenger/metabolism ; RNA, Plant
Chemical Substances	MicroRNAs ; RNA Precursors ; RNA, Messenger ; RNA, Plant ; RNA (63231-63-0)
Language	English
Publishing date	2005-10-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/j.febslet.2005.09.040
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Article: A postulated role for microRNA in cellular differentiation

Bentwich, Isaac

FASEB journal : 2005 Jun., v. 19, no. 8

2005

Abstract: ... Bentwich, I. A postulated role for microRNA in cellular differentiation. ...

Abstract	Over the past two decades a variety of mechanisms regulating cellular differentiation have been uncovered. These include signaling by morphogens or membrane-associated ligands and asymmetric segregation of cytoplasmic components. Most of these processes are driven by protein coding genes. Here I describe another possible cellular differentiation mechanism that involves asymmetric segregation of microRNAs, a group of recently discovered non-protein coding genes that have been shown to be involved in differentiation.--Bentwich, I. A postulated role for microRNA in cellular differentiation.
Language	English
Dates of publication	2005-06
Size	p. 875-879.
Document type	Article
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
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Article: Identification of hundreds of conserved and nonconserved human microRNAs.

Bentwich, Isaac / Avniel, Amir / Karov, Yael / Aharonov, Ranit / Gilad, Shlomit / Barad, Omer / Barzilai, Adi / Einat, Paz / Einav, Uri / Meiri, Eti / Sharon, Eilon / Spector, Yael / Bentwich, Zvi

Nature genetics

2005 Volume 37, Issue 7, Page(s) 766–770

Abstract: MicroRNAs are noncoding RNAs of approximately 22 nucleotides that suppress translation of target genes by binding to their mRNA and thus have a central role in gene regulation in health and disease. To date, 222 human microRNAs have been identified, 86 ... ...

Abstract	MicroRNAs are noncoding RNAs of approximately 22 nucleotides that suppress translation of target genes by binding to their mRNA and thus have a central role in gene regulation in health and disease. To date, 222 human microRNAs have been identified, 86 by random cloning and sequencing, 43 by computational approaches and the rest as putative microRNAs homologous to microRNAs in other species. To prove our hypothesis that the total number of microRNAs may be much larger and that several have emerged only in primates, we developed an integrative approach combining bioinformatic predictions with microarray analysis and sequence-directed cloning. Here we report the use of this approach to clone and sequence 89 new human microRNAs (nearly doubling the current number of sequenced human microRNAs), 53 of which are not conserved beyond primates. These findings suggest that the total number of human microRNAs is at least 800.
MeSH term(s)	Base Sequence ; Conserved Sequence ; Genome, Human ; Humans ; MicroRNAs/analysis ; Microarray Analysis ; Molecular Sequence Data ; Nucleic Acid Conformation ; Sequence Alignment ; Sequence Analysis, DNA
Chemical Substances	MicroRNAs
Language	English
Publishing date	2005-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/ng1590
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Article: Treatment of intestinal helminths does not reduce plasma concentrations of HIV-1 RNA in coinfected Zambian adults.

Modjarrad, Kayvon / Zulu, Isaac / Redden, David T / Njobvu, Lungowe / Lane, H Clifford / Bentwich, Zvi / Vermund, Sten H

The Journal of infectious diseases

2005 Volume 192, Issue 7, Page(s) 1277–1283

Abstract: Background: Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)-infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma ... ...

Abstract	Background: Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)-infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA.Methods. We conducted a prospective study of 54 HIV-1- and helminth-coinfected and 57 HIV-1-infected, helminth-uninfected asymptomatic adults living in Lusaka, Zambia, to assess the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA. Results: Median baseline viral load was 0.33 log(10) copies/mL lower in the helminth-infected group than in the uninfected group. Mean viral load between pretreatment and posttreatment visits increased in the helminth-infected (mean, 4.23 vs. 4.29 log(10) copies/mL; P=.6) and helminth-uninfected (mean, 4.39 vs. 4.52 log(10) copies/mL; P=.2) groups. Helminth-infected participants with high pretreatment viral loads had a mean 0.25-log(10) copies/mL decrease after treatment (P=.3), and helminth-uninfected participants had a mean 0.02-log(10) copies/mL decrease (P=.8). Conclusions: We did not find an overall association between treatment of intestinal helminth infections and reduction in viral load in coinfected adults. Future studies may need to focus on adults with intense helminth infections who live in rural areas or on adults or children who harbor higher helminth burdens and plasma concentrations of HIV-1 RNA.
MeSH term(s)	Adult ; Animals ; Anthelmintics/therapeutic use ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Female ; HIV Infections/complications ; HIV-1 ; Helminthiasis/complications ; Helminthiasis/drug therapy ; Humans ; Intestinal Diseases, Parasitic/complications ; Intestinal Diseases, Parasitic/drug therapy ; Male ; Prospective Studies ; RNA, Viral/blood ; Treatment Outcome ; Viral Load ; Zambia
Chemical Substances	Anthelmintics ; RNA, Viral
Language	English
Publishing date	2005-10-01
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1086/444543
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Article: MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues.

Barad, Omer / Meiri, Eti / Avniel, Amir / Aharonov, Ranit / Barzilai, Adi / Bentwich, Isaac / Einav, Uri / Gilad, Shlomit / Hurban, Patrick / Karov, Yael / Lobenhofer, Edward K / Sharon, Eilon / Shiboleth, Yoel M / Shtutman, Marat / Bentwich, Zvi / Einat, Paz

Genome research

2004 Volume 14, Issue 12, Page(s) 2486–2494

Abstract: MicroRNAs (MIRs) are a novel group of conserved short approximately 22 nucleotide-long RNAs with important roles in regulating gene expression. We have established a MIR-specific oligonucleotide microarray system that enables efficient analysis of the ... ...

Abstract	MicroRNAs (MIRs) are a novel group of conserved short approximately 22 nucleotide-long RNAs with important roles in regulating gene expression. We have established a MIR-specific oligonucleotide microarray system that enables efficient analysis of the expression of the human MIRs identified so far. We show that the 60-mer oligonucleotide probes on the microarrays hybridize with labeled cRNA of MIRs, but not with their precursor hairpin RNAs, derived from amplified, size-fractionated, total RNA of human origin. Signal intensity is related to the location of the MIR sequences within the 60-mer probes, with location at the 5' region giving the highest signals, and at the 3' end, giving the lowest signals. Accordingly, 60-mer probes harboring one MIR copy at the 5' end gave signals of similar intensity to probes containing two or three MIR copies. Mismatch analysis shows that mutations within the MIR sequence significantly reduce or eliminate the signal, suggesting that the observed signals faithfully reflect the abundance of matching MIRs in the labeled cRNA. Expression profiling of 150 MIRs in five human tissues and in HeLa cells revealed a good overall concordance with previously published results, but also with some differences. We present novel data on MIR expression in thymus, testes, and placenta, and have identified MIRs highly enriched in these tissues. Taken together, these results highlight the increased sensitivity of the DNA microarray over other methods for the detection and study of MIRs, and the immense potential in applying such microarrays for the study of MIRs in health and disease.
MeSH term(s)	Base Sequence ; Cluster Analysis ; DNA Probes/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; HeLa Cells ; Humans ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis/methods ; Placenta/metabolism ; Sequence Alignment ; Testis/metabolism ; Thymus Gland/metabolism
Chemical Substances	DNA Probes ; MicroRNAs
Language	English
Publishing date	2004-12
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.2845604
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Article ; Online: MicroRNAs accurately identify cancer tissue origin.

Rosenfeld, Nitzan / Aharonov, Ranit / Meiri, Eti / Rosenwald, Shai / Spector, Yael / Zepeniuk, Merav / Benjamin, Hila / Shabes, Norberto / Tabak, Sarit / Levy, Asaf / Lebanony, Danit / Goren, Yaron / Silberschein, Erez / Targan, Nurit / Ben-Ari, Alex / Gilad, Shlomit / Sion-Vardy, Netta / Tobar, Ana / Feinmesser, Meora /

Kharenko, Oleg / Nativ, Ofer / Nass, Dvora / Perelman, Marina / Yosepovich, Ady / Shalmon, Bruria / Polak-Charcon, Sylvie / Fridman, Eddie / Avniel, Amir / Bentwich, Isaac / Bentwich, Zvi / Cohen, Dalia / Chajut, Ayelet / Barshack, Iris

Nature biotechnology

2008 Volume 26, Issue 4, Page(s) 462–469

Abstract: MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of ... ...

Abstract	MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of unknown primary origin arose, a major clinical problem. We measured miRNA expression levels in 400 paraffin-embedded and fresh-frozen samples from 22 different tumor tissues and metastases. We used miRNA microarray data of 253 samples to construct a transparent classifier based on 48 miRNAs. Two-thirds of samples were classified with high confidence, with accuracy >90%. In an independent blinded test-set of 83 samples, overall high-confidence accuracy reached 89%. Classification accuracy reached 100% for most tissue classes, including 131 metastatic samples. We further validated the utility of the miRNA biomarkers by quantitative RT-PCR using 65 additional blinded test samples. Our findings demonstrate the effectiveness of miRNAs as biomarkers for tracing the tissue of origin of cancers of unknown primary origin.
MeSH term(s)	Base Sequence ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Gene Expression Profiling/methods ; Humans ; MicroRNAs/genetics ; Molecular Sequence Data ; Neoplasms/diagnosis ; Neoplasms/genetics ; Oligonucleotide Array Sequence Analysis/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Tumor Cells, Cultured
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2008-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/nbt1392
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Article ; Online: Unsung hero Robert C. Gallo.

Abbadessa, Giovanni / Accolla, Roberto / Aiuti, Fernando / Albini, Adriana / Aldovini, Anna / Alfano, Massimo / Antonelli, Guido / Bartholomew, Courtenay / Bentwich, Zvi / Bertazzoni, Umberto / Berzofsky, Jay A / Biberfeld, Peter / Boeri, Enzo / Buonaguro, Luigi / Buonaguro, Franco M / Bukrinsky, Michael / Burny, Arsène / Caruso, Arnaldo / Cassol, Sharon /

Chandra, Prakash / Ceccherini-Nelli, Luca / Chieco-Bianchi, Luigi / Clerici, Mario / Colombini-Hatch, Sandra / de Giuli Morghen, Carlo / de Maria, Andrea / de Rossi, Anita / Dierich, Manfred / Della-Favera, Riccardo / Dolei, Antonina / Douek, Daniel / Erfle, Volker / Felber, Barbara / Fiorentini, Simona / Franchini, Genoveffa / Gershoni, Jonathan M / Gotch, Frances / Green, Patrick / Greene, Warner C / Hall, William / Haseltine, William / Jacobson, Stephens / Kallings, Lars O / Kalyanaraman, Vaniambadi S / Katinger, Hermann / Khalili, Kamel / Klein, George / Klein, Eva / Klotman, Mary / Klotman, Paul / Kotler, Moshe / Kurth, Reinhard / Lafeuillade, Alain / La Placa, Michelangelo / Lewis, Jonathan / Lillo, Flavia / Lisziewicz, Julianna / Lomonico, Anita / Lopalco, Lucia / Lori, Franco / Lusso, Paolo / Macchi, Beatrice / Malim, Michael / Margolis, Leonid / Markham, Phillip D / McClure, Myra / Miller, Nancy / Mingari, Maria C / Moretta, Lorenzo / Noonan, Douglas / O'Brien, Steve / Okamoto, Takashi / Pal, Ranajit / Palese, Peter / Panet, Amos / Pantaleo, Giuseppe / Pavlakis, George / Pistello, Mauro / Plotkin, Stanley / Poli, Guido / Pomerantz, Roger / Radaelli, Antonia / Robertguroff, Marjorie / Roederer, Mario / Sarngadharan, Mangalasseril G / Schols, Dominique / Secchiero, Paola / Shearer, Gene / Siccardi, Antonio / Stevenson, Mario / Svoboda, Jan / Tartaglia, Jim / Torelli, Giuseppe / Tornesello, Maria Lina / Tschachler, Erwin / Vaccarezza, Mauro / Vallbracht, Angelika / van Lunzen, Jan / Varnier, Oliviero / Vicenzi, Elisa / von Melchner, Harald / Witz, Isaac / Zagury, Daniel / Zagury, Jean-Francois / Zauli, Giorgio / Zipeto, Donato

Science (New York, N.Y.)

2009 Volume 323, Issue 5911, Page(s) 206–207

MeSH term(s)	Acquired Immunodeficiency Syndrome/diagnosis ; Acquired Immunodeficiency Syndrome/history ; Acquired Immunodeficiency Syndrome/virology ; HIV-1/growth & development ; HIV-1/isolation & purification ; History, 20th Century ; History, 21st Century ; Humans ; Nobel Prize ; United States
Language	English
Publishing date	2009-01-09
Publishing country	United States
Document type	Biography ; Historical Article ; Letter
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.323.5911.206
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