Biomarker identification
AssigneeImmunexpress Pty Ltd
InventorsRichard Bruce BRANDON, Leo Charles MCHUGH
Life of this patent
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Abstract
Disclosed are method and apparatus for identifying biomarkers and in particular for identifying biomarkers for use in making clinical assessments, such as early diagnostic, diagnostic, disease stage, disease severity, disease subtype, response to therapy or prognostic assessments. In one particular example, the techniques are applied to allow assessments of patients suffering from, suspected of suffering from, or with clinical signs of SIRS (Systemic Inflammatory Response Syndrome) being either infection-negative SIRS or infection-positive SIRS.
Claims50
1) Apparatus for identifying biomarkers, the apparatus including an electronic processing device that:
- a) uses reference data from a plurality of individuals to define a number of groups of individuals, the reference data including measurements of the activity of a plurality of reference biomarkers;
- b) uses a plurality of analysis techniques to identify a number of potential biomarkers from the plurality of reference biomarkers that are potentially useful for distinguishing the groups of individuals, allowing the potential biomarkers to be used in generating signatures for use in clinical assessments.
12) Apparatus according to any one of the claims 1 to 12, wherein the analysis techniques include:
- a) sparse PLS;
- b) random forest;
- and,
- c) support vector machines.
29) A method for determining the likelihood of the presence or absence of a condition selected from a healthy condition (e.g., a normal condition or one in which inSIRS and inSIRS are absent), SIRS generally (i.e., not distinguishing between inSIRS or ipSIRS), inSIRS or ipSIRS, or to assess the likelihood of the presence, absence or risk of development of a stage of ipSIRS (e.g., a stage of ipSIRS with a particular severity), the method comprising:
- (1) correlating a reference IRS biomarker profile with the presence or absence, or degree of a condition selected from a healthy condition, SIRS, inSIRS, ipSIRS, or a particular stage of ipSIRS, wherein the reference IRS biomarker profile evaluates at least one IRS biomarker;
- (2) obtaining an IRS biomarker profile of a sample from a subject, wherein the sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker;
- and (3) determining a likelihood of the subject having or not having the condition based on the sample IRS biomarker profile and the reference IRS biomarker profile, wherein an individual IRS biomarker is an expression product of an IRS biomarker gene selected from the group consisting of:
- TLR5;
- CD177;
- VNN1;
- UBE2J1;
- IMP3;
- RNASE2//LOC643332;
- CLEC4D;
- C3AR1;
- GPR56;
- ARG1;
- FCGR1A//FCGR1B//FCGR1C;
- C11orf82;
- FAR2;
- GNLY;
- GALNT3;
- OMG;
- SLC37A3;
- BMX//HNRPDL;
- STOM;
- TDRD9;
- KREMEN1;
- FAIM3;
- CLEC4E;
- IL18R1;
- ACER3;
- ERLIN1;
- TGFBR1;
- FKBP5//LOC285847;
- GPR84;
- C7orf53;
- PLB1;
- DSE;
- PTGDR;
- CAMK4;
- DNAJC13;
- TNFAIP6;
- FOXD4L3//FOXD4L6//FOXD4//FOXD4L1//FOXD4L2//FOXD4L4//FOXD4L5;
- MMP9//LOC100128028;
- GSR;
- KLRF1;
- SH2D1B;
- ANKRD34B;
- SGMS2;
- B3GNT5//MCF2L2;
- GK3P//GK;
- PFKFB2;
- PICALM;
- METTL7B;
- HIST1H4C;
- C9orf72;
- HIST1H3I;
- SLC15A2;
- TLR10;
- ADM;
- CD274;
- CRIP1;
- LRRN3;
- HLA-DPB1;
- VAMP2;
- SMPDL3A;
- IF116;
- JKAMP;
- MRPL41;
- SLC1A3;
- OLFM4;
- CASS4;
- TCN1;
- WSB2;
- CLU;
- ODZ1;
- KPNA5;
- PLAC8;
- CD63;
- HPSE;
- C1orf161;
- DDAH2;
- KLRK1//KLRC4;
- ATP13A3;
- ITK;
- PMAIP1;
- LOC284757;
- GOT2;
- PDGFC;
- B3GAT3;
- HIST1H4E;
- HPGD;
- FGFBP2;
- LRRC70//IPO11;
- TMEM144//LOC285505;
- CDS2;
- BPI;
- ECHDC3;
- CCR3;
- HSPC159;
- OLAH;
- PPP2R5A//SNORA16B;
- TMTC1;
- EAF2//HCG11//LOC647979;
- RCBTB2//LOC100131993;
- SEC24A//SAR1B;
- SH3PXD2B;
- HMGB2;
- KLRD1;
- CHI3L1;
- FRMD3;
- SLC39A9;
- GIMAP7;
- ANAPC11;
- EXOSC4;
- gene for IL-1beta-regulated neutrophil survival protein as set forth in GenBank Accession No. AF234262;
- INSIG1;
- FOLR3//FOLR2;
- RUNX2;
- PRR13//PCBP2;
- HIST1H4L;
- LGALS1;
- CCR1;
- TPST1;
- HLA-DRA;
- CD163;
- FFAR2;
- PHOSPHO1;
- PPIF;
- MTHFS;
- DNAJC9//FAM149B1//RPL26;
- LCN2;
- EIF2AK2;
- LGALS2;
- SIAE;
- AP3B2;
- ABCA13;
- gene for transcript set forth in GenBank Accession No. AK098012;
- EFCAB2;
- HIST1H2AA;
- HINT1;
- HIST1H3J;
- CDA;
- SAP30;
- AGTRAP;
- SUCNR1;
- MTRR;
- PLA2G7;
- AIG1;
- PCOLCE2;
- GAB2;
- HS2ST1//UBA2;
- HIST1H3A;
- C22orf37;
- HLA-DPA1;
- VOPP1//LOC100128019;
- SLC39A8;
- MKI67;
- SLC11A1;
- AREG;
- ABCA1;
- DAAM2//LOC100131657;
- LTF;
- TREML1;
- GSTO1;
- PTGER2;
- CEACAM8;
- CLEC4A;
- PMS2CL//PMS2;
- RETN;
- PDE3B;
- SULF2;
- NEK6//LOC100129034;
- CENPK;
- TRAF3;
- GPR65;
- IRF4;
- MACF1;
- AMFR;
- RPL17//SNORD58B;
- IRS2;
- JUP;
- CD24;
- GALNT2;
- HSP90AB1//HSP90AB3P//HSP90AB2P;
- GLT25D1;
- OR9A2;
- HDHD1A;
- ACTA2;
- ACPL2;
- LRRFIP1;
- KCNMA1;
- OCR1;
- ITGA4//CERKL;
- EIF1AX//SCARNA9L//EIF1AP1;
- SFRS9;
- DPH3;
- ERGIC1;
- CD300A;
- NF-E4;
- MINPP1;
- TRIM21;
- ZNF28;
- NPCDR1;
- gene for protein FLJ21394 as set forth in GenBank Accession No. BC013935;
- gene for transcript set forth in GenBank Accession No. AK000992;
- ICAM1;
- TAF13;
- P4HA1//RPL17;
- C15orf54;
- KLHL5;
- HAL;
- DLEU2//DLEU2L;
- ANKRD28;
- LY6G5B//CSNK2B;
- KIAA1257//ACAD9//LOC100132731;
- MGST3;
- KIAA0746;
- HSPB1//HSPBL2;
- CCR4;
- TYMS;
- RRP12//LOC644215;
- CCDC125;
- HIST1H2BM;
- PDK4;
- ABCG1;
- IL1B;
- THBS1;
- ITGA2B;
- LHFP;
- LAIR1//LAIR2;
- HIST1H3B;
- ZRANB1;
- TIMM10;
- FSD1L//GARNL1;
- HIST1H2AJ//HIST1H2AI;
- PTGS1;
- gene for transcript set forth in GenBank Accession No. BC008667;
- UBE2F//C20orf194//SCLY;
- HIST1H3C;
- FAM118A;
- CCRL2;
- E2F6;
- MPZL3;
- SRXN1;
- CD151;
- HIST1H3H;
- FSD1L;
- RFESD//SPATA9;
- TPX2;
- S100B;
- ZNF587//ZNF417;
- PYHIN1;
- KIAA1324;
- CEACAM6//CEACAM5;
- APOLD1;
- FABP2;
- KDM6B//TMEM88;
- IGK@//IGKC//IGKV1-5//IGKV3D-11//IGKV3-20//IGKV3D-15//LOC440871//LOC652493//LOC100291464//LOC652694//IGKV3-15//LOC650405//LOC100291682;
- MYL9;
- HIST1H2BJ;
- TAAR1;
- CLC;
- CYP4F3//CYP4F2;
- CEP97;
- SON;
- IRF1;
- SYNE2;
- MME;
- LASS4;
- DEFA4//DEFA8P;
- C7orf58;
- DYNLL1;
- gene for transcript set forth in GenBank Accession No. AY461701;
- MPO;
- CPM;
- TSHZ2;
- PLIN2;
- FAM118B;
- B4GALT3;
- RASA4//RASA4P//RASA4B//POLR2J4//LOC100132214;
- CTSL1//CTSLL3;
- NP;
- ATF7;
- SPARC;
- PLB1;
- C4orf3;
- POLE2;
- TNFRSF17;
- FBXL13;
- PLEKHA3;
- TMEM62//SPCS2//LOC653566;
- RBP7;
- PLEKHF2;
- RGS2;
- ATP6V0D1//LOC100132855;
- RPIA;
- CAMK1D;
- IL1RL1;
- CMTM5;
- AIF1;
- CFD;
- MPZL2;
- LOC100128751;
- IGJ;
- CDC26;
- PPP1R2//PPP1R2P3;
- IL5RA;
- ARL17P1//ARL17;
- ATP5L//ATP5L2;
- TAS2R31;
- HIST2H2BF//HIST2H3D;
- CALM2//C2orf61;
- SPATA6;
- IGLV6-57;
- C1orf128;
- KRTAP15-1;
- IF144;
- IGL@//IGLV1-44//LOC96610//IGLV2-23//IGLC1//IGLV2-18//IGLV5-45//IGLV3-25//IGLV3-12//IGLV1-36//IGLV3-27//IGLV7-46//IGLV4-3//IGLV3-16//IGLV3-19//IGLV7-43//IGLV3-22//IGLV5-37//IGLV10-54//IGLV8-61//LOC651536;
- gene for transcript set forth in GenBank Accession No. BC034024;
- SDHC;
- NFXL1;
- GLDC;
- DCTN5;
- and KIAA0101//CSNK1G1
40) A method for treating, preventing or inhibiting the development of inSIRS, ipSIRS or a particular stage of ipSIRS in a subject, the method comprising:
- (1) correlating a reference IRS biomarker profile with the presence or absence of a condition selected from a healthy condition, SIRS, inSIRS, ipSIRS, or a particular stage of ipSIRS, wherein the reference IRS biomarker profile evaluates at least one IRS biomarker;
- (2) obtaining an IRS biomarker profile of a sample from a subject, wherein the sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker;
- (3) determining a likelihood of the subject having or not having the condition based on the sample IRS biomarker profile and the reference IRS biomarker profile, and administering to the subject, on the basis that the subject has an increased likelihood of having inSIRS, an effective amount of an agent that treats or ameliorates the symptoms or reverses or inhibits the development of inSIRS, or administering to the subject, on the basis that the subject has an increased likelihood of having ipSIRS or a particular stage of ipSIRS, an effective amount of an agent that treats or ameliorates the symptoms or reverses or inhibits the development of ipSIRS or the particular stage of ipSIRS.
41) A method of monitoring the efficacy of a particular treatment regimen in a subject towards a desired health state (e.g., healthy condition), the method comprising:
- (1) providing a correlation of a reference IRS biomarker profile with the likelihood of having a healthy condition;
- (2) obtaining a corresponding IRS biomarker profile of a subject having inSIRS, ipSIRS or a particular stage of ipSIRS after treatment with a treatment regimen, wherein a similarity of the subject's IRS biomarker profile after treatment to the reference IRS biomarker profile indicates the likelihood that the treatment regimen is effective for changing the health status of the subject to the desired health state.
42) A method of correlating a reference IRS biomarker profile with an effective treatment regimen for a condition selected from inSIRS, ipSIRS or a particular stage of ipSIRS, wherein the reference IRS biomarker profile evaluates at least one IRS biomarker, the method comprising:
- (a) determining a sample IRS biomarker profile from a subject with the condition prior to treatment, wherein the sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker;
- and correlating the sample IRS biomarker profile with a treatment regimen that is effective for treating the condition.
43) A method of determining whether a treatment regimen is effective for treating a subject with a condition selected from inSIRS, ipSIRS or a particular stage of ipSIRS, the method comprising:
- (a) correlating a reference biomarker profile prior to treatment with an effective treatment regimen for the condition, wherein the reference IRS biomarker profile evaluates at least one IRS biomarker;
- and (b) obtaining a sample IRS biomarker profile from the subject after treatment, wherein the sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker, and wherein the sample IRS biomarker profile after treatment indicates whether the treatment regimen is effective for treating the condition in the subject.
44) A method of correlating an IRS biomarker profile with a positive or negative response to a treatment regimen, the method comprising:
- (a) obtaining an IRS biomarker profile from a subject with a condition selected from inSIRS, ipSIRS or a particular stage of ipSIRS following commencement of the treatment regimen, wherein the IRS biomarker profile evaluates at least one IRS biomarker;
- and (b) correlating the IRS biomarker profile from the subject with a positive or negative response to the treatment regimen.
45) A method of determining a positive or negative response to a treatment regimen by a subject with a condition selected from inSIRS, ipSIRS or a particular stage of ipSIRS, the method comprising:
- (a) correlating a reference IRS biomarker profile with a positive or negative response to the treatment regimen, wherein the reference IRS biomarker profile evaluates at least one (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) IRS biomarker;
- and (b) determining a sample IRS biomarker profile from the subject, wherein the subject's sample IRS biomarker profile evaluates for an individual IRS biomarker in the reference IRS biomarker profile a corresponding IRS biomarker and indicates whether the subject is responding to the treatment regimen.
Dependencies are inferred from the claim text.